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GUT Year 1 > SEM2 > Flashcards

SEM2 Flashcards

1
Q

What is neuropeptide Y?

A

An orexigenic factor that induces desire to eat (appetite). It’s synthesised in GABAergic neurones and is majorly expressed in interneurons

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2
Q

What’s AgRP?

A

Agouti-related peptide is a neuropeptide produced in the brain by the AgRP/NPY neuron. It increases appetite and decreases metabolism and energy expenditure.

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3
Q

Where is AgRP synthesised?

A

Neuropeptide Y-containing cell bodies in the ventromedial part of the arcuate nucleus in the hypothalamus

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4
Q

What’s the pharmacokinetics of AgRP?

A

AgRP acts as an antagonist to MCR4 (Melanocortin 4 receptor), a G-protein-coupled receptor that binds alpha-melanocyte stimulating hormone (a-MSH)

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5
Q

What receptors does neuropeptide Y bind to? (4 options)

A

Y1, Y2, Y4 or Y5

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6
Q

What is POMC?

A

Proopiomelanocortin is the pituitary precursor of circulating alpha-melanocyte stimulating hormone, ACTH and ß-endorphin.

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7
Q

Where is POMC synthesised?

A

In corticotrophins of the anterior pituitary (from pre-proopiomelanocortin)

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8
Q

What receptors does 5HT bind to to promote metabolism of POMC?

A

5HT2C

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9
Q

What happens when 5HT triggers metabolism of POMC?

A

The metabolism leads to a-MSH release onto MCR4 receptors to decrease appetite

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10
Q

Name a 5HT2C agonist

A

Meta-chlorophenylpiperazine (mCPP) is a 5HT2C agonist

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11
Q

What is zimeldine?

A

Zimeldine is an SSRI (selective serotonin reuptake inhibitor)

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12
Q

What does zimeldine do?

A

It blocks 5HT reuptake at the serotonin reuptake pump of the neuronal membrane in the CNS, enhancing its actions on 5HT1A autoreceptors

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13
Q

Where is the satiety centre?

A

The ventromedial wall of the paraventricular nuclei in the hypothalamus

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14
Q

What happens when the ventromedial nuclei are stimulated?

A

It causes aphagia

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15
Q

What is the feeding/hunger/thirst centre of the brain?

A

The lateral hypothalamus

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16
Q

What happens when the lateral hypothalamus is stimulated?

A

Feeding/ appetite is increased

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17
Q

How do opioids and growth hormone-releasing hormone affect appetite?

A

They increase appetite

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18
Q

What is naltrexone?

A

An opioid antagonist that reduces the positive ‘hedonic valence’ of food, therefore decreasing appetite

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19
Q

How does blood glucose concentration affect hunger?

A

High BGC stimulates gluco-receptors in the hypothalamus and cause satiety, while low BGC up-regulates hunger

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20
Q

How does afferent input affect hunger?

A

Distension of the stomach inhibits appetite, while contraction of an empty stomach stimulates appetite

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21
Q

How does fat ingestion affect appetite?

A

Fat in the duodenum causes CCK release from I cells, which slow gastric emptying for satiety.

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22
Q

How does the amount of stored white fat affect insulin release from ß-cells?

A

With more white adipose stores, more insulin is released

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23
Q

How does insulin affect appetite?

A

Some insulin released into circulation will flow through brain capillaries to the brain. Here, insulin usually reduces appetite by down-regulating NPY and AgRP in a catabolic response. Insulin can also act on POMC/CART neurons to increase food intake

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24
Q

How does glucagon act as an anorexigenic agent?

A

It acts on the hindbrain via the liver to promote release of glucose and inhibition of food intake

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25
Q

Where are leptin genes expressed?

A

Mainly in adipocytes

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26
Q

What 3 things does leptin do?

A

Decrease food intake, induce weight loss and increase energy expenditure

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27
Q

How does leptin act as a lipostat?

A

It controls fat stores by operating a feedback mechanism between adipose tissue and the arcuate nucleus in the brain.

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28
Q

What does leptin increase the expression of?

A

Anorexigenic agents like POMC, cocaine- and amphetamine-regulated transcript (CART), CRH and neurotensin)

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29
Q

What does leptin inhibit to decrease appetite?

A

NPY

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30
Q

What is ghrelin?

A

A fast-acting orexin that stimulates hunger and foo intake

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31
Q

What 3 organs release ghrelin?

A

The pancreas, stomach and adrenal glands

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32
Q

When do circulating ghrelin levels rise and fall?

A

Ghrelin levels are high pre-prandially, then drop after a meal.

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33
Q

How does ghrelin generate hunger signals?

A

Ghrelin increases central orexin like NPY and AgRP, and suppresses the ability of leptin to stimulate anorexigenic factors

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34
Q

What can inhibit ghrelin secretion?

A

Leptin

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35
Q

What cells produce obestatin?

A

Epithelial cells of the stomach

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36
Q

What does obestatin do?

A

Obestatin suppresses food intake through appetite, so it antagonises ghrelin-induced foo intake and growth hormone secretion

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37
Q

What is hunger?

A

Discomfort caused by lack of food and by the desire to eat. A strong physiological drive for food. A sensation of emptiness of the stomach

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38
Q

What is appetite?

A

Physiological desire/ drive to satisfy the body’s need for food

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39
Q

What is satiety?

A

The state of being full after eating

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40
Q

What are the 3 stages f stomach activity?

A

Fasting, accommodation and emptying

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41
Q

What is aphagia?

A

The inability or refusal to swallow

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42
Q

What is hyperphagia/polyphagia?

A

An abnormal desire for food (extreme unsatisfied drive to eat)

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43
Q

What 5 hypothalamic sites are involved in feeding behaviour/ food intake?

A 
The lateral hypothalamus (LH)
The ventromedial nucleus (VMN)
The dorsomedial nucleus (DMN)
The paraventricular nucleus (PVN)
The arcuate nucleus
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44
Q

What is a microbiota?

A

The microorganisms of a particular site, habitat or geological period

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45
Q

What is a microbiome?

A

The microorganisms in a particular environment.

The combined genetic material of the microorganisms in a particular environment

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46
Q

What are resident flora?

A

The normal bacteria of the body that we have for life

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47
Q

What are transient flora?

A

Bacteria of the body that can be modified by diet, environment, stress, hormones, age and transit time

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48
Q

What makes up around 90% of the bacteria in babies?

A

Bifidobacterium

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49
Q

Why is bifidobacteria so important in babies?

A

These bacteria utilise the oligosaccharides from breast milk, so they create the right environment for a neonate’s gut

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50
Q

What is the first passage from the rectum?

A

Sterile meconium

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51
Q

What does normal flora shift to after weaning?

A

Bifidobacter is reduced, and bacteroides, clostridia and eubacteria increase

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52
Q

Roughly how many bacteria are there in the duodenum and jejunum?

A

Around 1000/g

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53
Q

How many bacteria are there in the ileum?

A

Around 10^8-10^10/g

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54
Q

What conditions can disruption of the normal flora lead to (dysbiosis)?

A

IBD, IBS, clostridium difficile, colon cancer, coeliac disease, diabetes

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55
Q

What is clostridium difficile?

A

A bacterium that can infect the bowel and cause diarrhoea, most commonly infecting people who have recently been treated with antibiotics.

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56
Q

What are the most common symptoms of C. diff?

A

Diarrhoea, painful abdominal cramps, nausea, dehydration, fever, loss of appetite and weight loss

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57
Q

Name 4 benefits of the presence of gut flora

A

Colonisation resistance- blocks pathogens
Produce metabolites of benefit to the host- vitamin K2 and B12
Normal development of immunity- tolerance nd antigenic stimulation
Gut flora aids digestion- fermentation of sugars and regulation of fat storage

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58
Q

What are the main bacteria in the duodenum and jejunum?

A

Lactocilli and Streptococci

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59
Q

What are the bacteria in the ileum?

A

There are Bacteriodes and E. coli

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60
Q

What bacteria are there I the colon?

A

Obligate anaerobes like Bacteriodes, Clostridia and Bifidibacter, and facultative anaerobes like E. coli

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61
Q

What’s pseudomembranous colitis?

A

Swelling or inflammation of the large intestine due to an overgrowth of C. difficile bacteria.

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62
Q

How does pseudomembranous colitis present in mild cases?

A

It may appear as minimal inflammation or oedema of the colonic mucosa

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63
Q

How does pseudomembranous colitis present in more severe cases?

A

The mucosa is often covered with loosely adherent nodular or diffuse exudates. These raised exudative plaques are 2-5mm in size. Coalescence of these plaques generates an endoscopic appearance of yellowish pseudomembranes lining the colonic mucosa

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64
Q

What’s the clinical definition of diarrhoea?

A

Watery or liquid stools, usually with an increase in stool weight above 200g per day and an increase in daily stool frequency and often a sense of urgency

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65
Q

What are the clinical consequences of diarrhoea?

A

It can lead to severe dehydration. Excessive fluid and electrolyte loss, hypovolaemia, hypokalaemia and organ failure are possible.
It can cause reduced growth.

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66
Q

What is dysentry?

A

Infection of the intestines resulting in severe diarrhoea with the presence of blood and mucus in the faeces

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67
Q

What are the symptoms of dysentry?

A

Blood and mucus in the faeces, pain, fever and abdominal cramps

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68
Q

What bacterium is the main cause of dysentry?

A

Shigella

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69
Q

How do enterotoxins affect the pharmacology of enterocytes?

A

They affect fluid and electrolyte transport by changing intracellular signalling molecules (exotoxins) or damaging endothelial cell membranes (cytotoxins)

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70
Q

What are enterocytes?

A

Simple columnar epithelial cells which line the inner surface of the small and large intestines, with a glycocalyx coat and microvilli on their apical surface

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71
Q

How can bacteria damage epithelium besides their toxins?

A

Bacteria can adhere to epithelium and damage the brush border of enterocytes by effacement of the apical membrane. This stops absorption of nutrients, resulting in anti-absorptive diarrhoea

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72
Q

What type of epithelial cells line the oesophagus?

A

Striated squamous epithelial cells

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73
Q

What levels does the oesophagus run from?

A

C6 to T12

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74
Q

What kind of muscle is in the musculo-cartilaginous structure that is the upper oesophageal sphincter?

A

Striated muscle

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75
Q

When does the UOS constrict?

A

To avoid air entering the oesophagus when you inhale

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76
Q

What muscle makes up the LOS?

A

Smooth muscle

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77
Q

What is the intrinsic component of the LOS?

A

Thick, circular, oesophageal smooth muscles under neurohormonal influence

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78
Q

What is the extrinsic component of the LOS?

A

The diaphragm

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79
Q

What does malfunction of the intrinsic and extrinsic components of the LOS lead to?

A

GORD

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80
Q

What are the 3 muscular intrinsic components of the LOS?

A

Thick circular smooth muscle layers
Clasp-like semi-circular smooth muscle fibres that encircle the gastrooesophageal junction medially on the right side.
Sling-like oblique gastric muscle fibres on the left lateral side that help to prevent regurgitation

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81
Q

What is the angle of His?

A

The oblique angle of the oesophagus as it meets the cardiac orifice of the stomach

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82
Q

What is the extrinsic component of the LOS and what’s its mechanism of action?

A

The crural diaphragm that encircles the LOS and forms a channel
Fibres of the crural portion of the diaphragm possess a ‘pinchcock-like’ action and have myogenic tone

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83
Q

What creates the oesophageal hiatus?

A

A loop of the right crux of the diaphragm

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84
Q

What 2 neurotransmitters control contraction of the intrinsic sphincters?

A

ACh and substance P

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85
Q

What 2 neurotransmitters control relaxation of the intrinsic sphincters?

A

NO and VIP

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86
Q

What innervates the striated muscle of the upper oesophagus?

A

Somatic motor neurones of the vagus nerve

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87
Q

What innervates the smooth muscle of the lower oesophagus?

A

Visceral motor neurones of the vagus nerve

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88
Q

Where does integration of impulses to the oesophagus occur?

A

The NTS, nucleus ambiguous and dorsal vagal nucleus

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89
Q

What are the 2 functions of the oesophagus?

A

Swallowing

Convey food and fluids from the pharynx to the stomach

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90
Q

What triggers swallowing?

A

Afferent impulses in the trigeminal, glossopharyngeal and vagus nerves

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91
Q

How do efferent impulses pass to the pharyngeal musculature and the tongue?

A

Via the trigeminal, facial and hypoglossal nerves

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92
Q

What are the voluntary and involuntary parts of swallowing?

A

The voluntary part is movement of food from the tongue backwards into the pharynx by skeletal muscle. Waves of involuntary contractions then push the material into the oesophagus

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93
Q

What is primary peristalsis in the oesophagus?

A

The ring of peristaltic waves behind the bolus at 4cm/s that move it towards the stomach

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94
Q

What is secondary peristalsis in the oesophagus?

A

The second wave that moves any for remnants along

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95
Q

What causes oropharyngeal dysphagia?

A

The inability to open the UOS or discooridnation of the timing between opening it and the pharyngeal push of the ingested bolus

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96
Q

What happens after you’ve swallowed something, involving the epiglottis?

A

The glottis opens and breathing can resume

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97
Q

Why is secondary peristalsis important for a large bolus?

A

A large bolus doesn’t reach the stomach after the first peristaltic wave. Distension of the oesophageal lumen stimulates receptors to cause secondary peristalsis

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98
Q

What 3 things prevent reflux of the gastric contents?

A

The LOS closes after material has passed
The ‘pinchcock’ effect of the diaphragmatic sphincter on the lower oesophagus
Plug-like action of the mucosal folds in the cardia occludes the lumen of the gastrooesophageal junction

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99
Q

What is achalasia?

A

A disorder of motility or peristalsis of the oesophagus whereby the LOS fails to open and normal peristaltic muscle activity is reduced

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100
Q

What is GORD?

A

Gastro-oesophageal reflux disease caused by a weak LOS

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101
Q

What is aphagia?

A

Swallowing difficulty

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102
Q

What is oesophageal spasm?

A

Abnormal oesophageal contractions that mean food isn’t effectively reaching the stomach

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103
Q

What is diffuse oesophageal spasm?

A

Chest pain coming from the oesophagus due to uncoordinated contractions

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104
Q

What is achalasia caused by?

A

It’s caused by impaired LOS relaxation, which can be accompanied by impaired peristalsis. Food and liquids fail to reach the stomach, resulting in dilation of the lower oesophagus. There’s a long period of sporadic dysphagia before food is regurgitated

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105
Q

What is the possible aetiology of achalasia?

A

Damage to the innervation of the oesophagus whereby there’s degenerative lesions to the vagus nerve and loss of the myenteric plexus ganglionic cells in the oesophagus. The initiating factor is unknown, although it’s thought to be autoimmune or triggered by infection

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106
Q

Give 5 symptoms of achalasia

A 
Dysphagia (because the LOS fails to relax enough to allow food into the stomach)
Vomiting
Weight loss
Failure to thrive
Heartburn
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107
Q

After hearing the patient’s description of their problems, what 2 diagnostic steps could you take?

A

Barium radiography

Oesophageal manometry for absent peristalsis

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108
Q

What is bird beak deformity a sign of regarding the oesophagus?

A

Tapering of the lower oesophagus in achalasia

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109
Q

What is oesophageal manometry used for?

A

To determine the cause of non-cardiac chest pain, to evaluate the cause of GOR, and to determine the cause of dysphagia.

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110
Q

What does the oesophageal manometry test involve?

A

A thin, pressure-sensitive tube is passed through the nose, along the pharynx, through the oesophagus into the stomach. When you swallow, the pressure-sensitive tube monitors the strength and coordination of muscle contractions and of relaxation of the LOS

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111
Q

What does low LOS pressure suggest from oesophageal manometry?

A

GORD

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112
Q

What is normal LOS pressure?

A

<26mmHg

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113
Q

What LOS pressure is considered achalasia?

A

> 100mmHg

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114
Q

What LOS pressure is considered nutcracker achalasia?

A

> 200mmHg

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115
Q

What does the patient do once the pressure-sensitive catheter is in place?

A

Take a deep breath and swallow water

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116
Q

What are the 2 most common types of oesophageal cancer?

A

Oesophageal adenocarcinoma

Squamous carcinoma

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117
Q

Where does oesophageal adenocarcinoma begin?

A

The mucus-secreting glands, usually in the lower oesophagus

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118
Q

Where does oesophageal squamous carcinoma most often occur?

A

In the upper and middle portions of the oesophagus

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119
Q

How are young people with low surgical risk treated for achalasia?

A

Laparoscopic Heller’s myotomy

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120
Q

How are older patients with low surgical risk treated for achalasia?

A

Pneumatic dilation

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121
Q

How are patients with high surgical risk treated for achalasia?

A

Botulinum toxin injection or Ca2+ blockers if this fails

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122
Q

Describe GORD

A

The retrograde movement of gastric contents into the oesophagus due to relaxation of the LOS

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123
Q

Why does gastro-oesophageal reflux usually stimulate salivation?

A

Saliva is an effective natural antacid, so it dilutes and neutralises refluxed gastric contents to decrease damage caused

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124
Q

What are around 98% of reflux events in normal individuals associated with?

A

Transient spontaneous relaxation of the LOS

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125
Q

What happens when the resting LOS pressure is too weak to resist the pressure within the stomach?

A

Sudden relaxation of the LOS that isn’t induced by swallowing

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126
Q

What are 3 factors that contribute to GORD severity?

A

Weak or uncontrolled oesophageal contractions
Length of time the oesophagus is exposed to gastric acid
Amount of pressure placed on the anti-reflux barrier

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127
Q

Name some lifestyle factors associated with GORD

A

Pregnancy, obesity, fatty food, coffee, alcohol, large meals, orange juice, onions, cigarettes and certain drugs

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128
Q

How can GORD lead to basal cell hyperplasia?

A

Desquamation of the oesophageal squamous mucosal cells from acid reflux and resulting cell loss

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129
Q

What can excessive desquamation of oesophageal mucosal cells lead to?

A

Ulceration

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130
Q

What is Barrett’s oesophagus?

A

Where stratified squamous epithelium of the oesophagus changes to simple columnar epithelium with interspersed goblet cells. This change is considered premalignant, as it’s associated with increased incidence of oesophageal adenocarcinoma

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131
Q

What are the pathophysiological and clinical features of GORD?

A

Low or absent resting LOS tone
LOS tone fails to increase when lying flat or during pregnancy
Poor oesophageal peristalsis leads to decreased acid clearance

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132
Q

How can a hiatus hernia affect LOS function?

A

A hiatal hernia can impair the function of the LOS and diaphragmatic closing mechanisms, giving symptoms similar to GORD

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133
Q

Give 3 symptoms of GORD

A

Heart burn and acid regurgitation
Nocturnal awakenings
Dysphagia

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134
Q

What is the first line of investigation of GORD?

A

Low dose proton pump inhibitor challenge

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135
Q

What are further steps for investigation of GORD?

A

Upper GI endoscopy, manometry or 24-hour ambulatory pH monitoring

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136
Q

How does pregnancy affect or induce GORD?

A

A foetus increases the pressure on the abdominal contents, pushing terminal segments of the oesophagus into the thoracic cavity. The last trimester of pregnancy is associated with increased abdominal pressure that forces gastric contents into the oesophagus. Heartburn subsides in the last months as the uterus descends into the pelvis

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137
Q

What causes heartburn in the absence of pregnancy?

A

Less efficient LOS that allows gastric contents to episodically reflux into the oesophagus.

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138
Q

Name 6 potential long-term effects of GORD

A 
Oesohpagitis
Oesophageal strictures
Squamous cell carcinoma
Barrett's oesophagus
Oesophageal adenocarcinoma
Oesophageal ulcers
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139
Q

Name some lifestyle changes for someone with GORD

A 
Raise the head of the bed for better sleep.
Lose weight
Decrease intake of trigger foods
Avoid large meals
Avoid lying down after meals
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140
Q

What is Nissen fundoplication?

A

Surgery in which doctors wrap the funds around the LOS so that it strengthens the valve mechanism

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141
Q

What drugs can someone with GORD take?

A

Antacids
H2 receptor antagonists and proton pump inhibitors.
Metoclopramide/ domperidone to enhance peristalsis and aid clearance of gastric acid

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142
Q

What do antacids do in treatment of GORD?

A

Neutrlise gastric acid and increase the pH of the gastric lumen.
Inhibit peptic activity and stop acid secretion

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143
Q

What do magnesium salts cause?

A

Diarrhoea

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144
Q

What do aluminium salts cause?

A

Constipation

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145
Q

What cells synthesise bile?

A

Hepatocytes

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146
Q

What is the pathway of bile into the duodenum?

A

Bile drains through the left and right hepatic ducts into the cystic duct and into the gallbladder. It’s then secreted into the duodenal lumen via the common bile duct and the ampulla of Vater

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147
Q

What is the function of the gallbladder?

A

Storage and secretion of bile

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148
Q

What do pancreatic juices contain?

A

Bile salts, bile pigments and dissolved substances in alkaline electrolytes. This is due to joining of the pancreatic duct to the common bile duct prior to entry into the duodenum

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149
Q

What are bile canaliculi?

A

Small, thin, capillary-like tubes that collect bile secreted by hepatocytes. They empty into a series of progressively larger bile ductules and ducts

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150
Q

What do terminal bile ducts merge to form?

A

The left and right hepatic ducts, which merge to for the common bile duct

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151
Q

What are cholangiocytes?

A

Epithelial cells that line the bile ducts

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152
Q

What is glutathione?

A

GSH is an antioxidant capable of preventing damage to important cellular components that’s caused by reactive oxygen species such as free radicals, peroxides, lipid peroxides and heavy metals

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153
Q

What do bile ductules secrete in response to secretin in the postprandial period?

A

Ductules secrete IgA for mucosal protection, HCO3- and H2O

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154
Q

What 2 cell types secrete the components of bile?

A

Hepatocytes produce cholesterol, lecithin, bile acids and bile pigments. Epithelial cells of bile ducts produce bicarbonate-rich salt solution

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155
Q

What are 3 bile pigments?

A

Bilirubin, biliverdin and urobilin

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156
Q

When is bile secretion at its greatest?

A

During and after a meal

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157
Q

When does the sphincter of Oddi contract?

A

During periods of fasting

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158
Q

When does the sphincter of Oddi relax?

A

During and after meals

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159
Q

What substances are secreted across the bile canalicular membrane?

A

Bile acids, phosphatidylcholine, conjugated bilirubin, cholesterol and xenobiotics

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160
Q

Describe the composition of hepatic bile

A

97% water, then fractional cholesterol, lecithin, bile acids and bile pigments etc.

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161
Q

Describe the composition of gallbladder bile

A

89% water, then the rest is HCO3-, Cl-, Ca2+, Mg2+, Na2+, cholesterol, bilirubin, bile salts etc.

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162
Q

Where is bile concentrated?

A

In the gallbladder, where NaCl and H2O loss leads to increased solid content

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163
Q

What are bile acids made from?

A

Cholesterol

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164
Q

What are bile acids conjugated to once secreted into bile in the liver?

A

Glycine or taurine

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165
Q

Why are bile acids conjugated?

A

To help increase the ability of bile acids to be secreted and to decrease their cytotoxicity

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166
Q

What does bile acid conjugated with glycine form?

A

Glycocholic acid

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167
Q

What does bile acid conjugated with taurine form?

A

Taurochenodeoxycholic acid

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168
Q

What are the 4 major bile acids in humans?

A

Cholic acid, chenodeoxycholic acid
Deoxycholic acid
Lithocholic acid

169
Q

What are the major 5 functions of bile?

A

Elimination of cholesterol to bile acids
Reduction of precipitation of cholesterol in the gallbladder
Facilitate the absorption of fat-soluble vitamins (ADEK)
Regulate their own transport and metabolism via enterohepatic circulation
Facilitate the digestion of triglycerides

170
Q

What are the 3 phases of contraction of the gallbladder?

A

The cephalic phase, gastric phase and intestinal phase

171
Q

What is the cephalic phase of gallbladder contraction?

A

Taste, smell and the presence of food in the mouth generates impulses via the vagus nerve

172
Q

What is the gastric phase of gallbladder contractions?

A

Distension of the stomach generates impulses in the vagus nerve

173
Q

What is the intestinal phase of gallbladder contraction?

A

A major period of gallbladder emptying. Key mediators are CCK and secretin, in response to lipids and hyperacidity, respectively

174
Q

How does CCK affect bile secretion?

A

CCK directly and indirectly triggers contraction of the gallbladder and relaxation of the sphincter of Oddi

175
Q

What neurotransmitters relax the sphincter of Oddi?

A

NO and VIP (NANC neurones)

176
Q

How does secretin affect bile secretion?

A

Secretin stimulates duct cells in the liver to produce bile

177
Q

What effects do CCK and secretin have on the pancreas?

A

CCK induces enzyme-rich pancreatic juice secretion. Secretin causes secretion of HCO3- rich pancreatic juice

178
Q

Where are bile salts and lecithin synthesised?

A

The liver

179
Q

How are most bile salts reabsorbed?

A

Na+ bile salt coupled transporters

180
Q

What’s enterohepatic circulation?

A

Circulation of bile acids, bilirubin, drugs or other substances from the liver to bile, into the small intestine, being absorbed by enterocytes and transported back to the liver

181
Q

What causes cholesterol gallstones?

A

Excessive secretion of cholesterol from the liver and reabsorption of salt and water, giving increased cholesterol, which crystallises into stones

182
Q

What are the 2 types of gallstones?

A

Cholesterol gallstones

Calcium gallstones

183
Q

What are 3 causes of cholesterol gallstones?

A

Obesity
Decreased bile acids
Decreased phospholipids

184
Q

What causes calcium gallstones?

A

Increased conjugated bilirubin

185
Q

What are factors of gallstone formation?

A

Sequestered bile salts in the gallbladder
Decreased bile acids due to malabsorption or bile production problems
Chronic infection by bacteria that aid pigment stone formation
Super-Saturation of bile with cholesterol
Presence of nucleation factors or glycoprotein

186
Q

Where may large gallstones lodge?

A

The opening of the gallbladder

187
Q

What can happen when gallstones lodge in the ampulla of Vater?

A

Stoppage of bile and pancreatic secretions, so pressure builds up and causes decreased bile secretion, resulting in jaundice and possible nutritional deficiency

188
Q

How can gallstones be diagnosed?

A

Visualisation, either via ultrasonography or CT scanning of the right upper quadrant

189
Q

What is cholescintigraphy?

A

Administration of technetium-99m-labelled derivative of iminodiacetic acid to image the gall bladder and ducts

190
Q

What is endoscope retrograde cholangiopancreotography (ERCP)?

A

A technique used to visualise the biliary tree by injecting contrast media from an endoscope channel

191
Q

What proportion of gallstone cases are asymptomatic?

A

Around 85%

192
Q

What are possible symptoms of gallstones?

A

Acute cholecystitis
Cholestatic jaundice
Cholangitis

193
Q

What does gallstone in the cystic bile duct cause?

A

Painful gallbladder contractions

194
Q

What does gallstone blocking the common bile duct cause?

A

Pain and nausea, as well as lack of bile release and jaundice

195
Q

What does gallstone blocking the duodenal papilla cause?

A

Inappropriate activation of pancreatic zymogens

Acute pancreatitis

196
Q

What cations are found in gastric juice?

A

Na+, K+, Mg2+, H+

197
Q

What anions are found in gastric juice?

A

Cl-, HPO4 2-, SO4 2-

198
Q

What is the pH of gastric juice?

A

3.0

199
Q

What volume of gastric juice is secreted each day?

A

Around 2.5L

200
Q

What 3 things do the fundus and body of the stomach secrete?

A

Mucus, HCl and pepsinogen

201
Q

What is secreted less in the antrum and what is secreted more?

A

Less HCl is secreted, but more gastrin is secreted to stimulate HCl secretion in the fundus and body

202
Q

What are the cells that line the wall of the stomach and was do they secrete?

A

Parietal cells secrete HCl and intrinsic factor

203
Q

What do ECL cells secrete?

A

Enterochromaffin-like cells secrete paracrine agents such as histamine for local effects

204
Q

What cranial nerve is very important to acid secretion?

A

The vagus nerve

205
Q

How is gastric acid made in the stomach lumen?

A

HCO3- is exchanged for Cl- in the blood, decreasing acidity of venous blood from the stomach. Excess Cl- diffuses out into the stomach through Cl- channels as the H+ is pumped into the stomach lumen by K+ H+ ATPase pumps. The net effect is flow of HCl out of parietal cells into the stomach lumen

206
Q

What do non-parietal cells secrete?

A

Resting juice, which is similar to plasma, with a pH of 7.4

207
Q

What is mucus high in?

A

HCO3-, so it’s alkaline

208
Q

What’s the function of mucus secreted into the stomach?

A

It forms water-insoluble gel on the epithelial surface to protect against H+

209
Q

What is the function of rennin?

A

Rennin is an enzyme that curdles milk into a casein clot in some animals

210
Q

What does intrinsic factor prevent?

A

Pernicious anaemia, by aiding absorption of vitamin B12

211
Q

What are the 3 functions of stomach HCl?

A

Kill bacteria
Acid denaturation of digested food
Activate pepsinogen into pepsin

212
Q

What are the 3 phases of gastric secretion?

A

The cephalic phase, gastric phase and intestinal phase

213
Q

What regulates HCl secretion?

A

Neuronal pathways and duodenal hormones

214
Q

How are gastric secretions mediated in the cephalic phase?

A

The vagus nerve stimulates acid production and pepsin activation

215
Q

How are gastric secretions mediated in the gastric phase?

A

Local nervous secretory reflexes, vagal reflexes and gastrin-histamine stimulation

216
Q

What elicits HCl secretion in the cephalic phase?

A

ACh release stimulates histamine release from ECL cells, as well as acting directly on parietal cells

217
Q

How does the gastric phase cause HCl secretion?

A

Distension of the stomach activates neural reflexes, causing ACh release from enteric neurons onto parietal cells. Peptides cause G cells to secrete gastrin that triggers histamine release from ECL cells and HCl release from parietal cells.

218
Q

What hormone inhibits gastrin, histamine and HCl secretion?

A

Somatostatin from D cells

219
Q

Why can excessive protein in the diet lead to stomach ulcers?

A

Hyperacidity. Proteins remove the inhibitory powers of HCl on gastrin secretion and hence acid secretion, so they increase gastrin-mediated acid secretion

220
Q

In the intestinal phase, what does high acidity of the duodenal contents cause?

A

An inhibitory reflex on acid secretion to prevent chyme from becoming too acidic

221
Q

What 4 things inhibit acid secretion in the intestinal phase?

A 
Distension of the duodenum
Hypertonic solution
Amino acids
Fatty acids
(Therefore the composition and volume of chyme)
222
Q

What causes the release of enterogastrones?

A

Acidity, distension, changes in osmolarity and presence of fats in the duodenum

223
Q

What are enterogastrones?

A

CCK, secretin, glucagon-like peptide-1 (GLP1) and gastrin-inhibiting peptide (GIP)

224
Q

What receptors does gastrin bind to on parietal cells and ECL cells?

A

CCKB (AKA CCK2)

225
Q

What receptors does ACh act on in the gut?

A

M3

226
Q

What receptors does histamine act on on parietal cells?

A

H2 receptors

227
Q

What type of receptor are H2 receptors?

A

Gs-mediated receptors that activate the A pathway

228
Q

What kind of receptors are somatostatin and prostaglandin receptors?

A

Gi-mediated receptors that inhibit the A pathway

229
Q

What 3 effects do prostaglandins have on the gut?

A

They inhibit parietal cell activity, promote bicarbonate secretion and promote mucus secretion

230
Q

What does HCl concentration depend on?

A

Rate of secretion, amount of buffering, composition of ingested food, rate of gastric emptying and amount of diffusion back into mucosa

231
Q

What is hypochlorhydria/achlorhydria?

A

Absence of or low HCl production in gastric secretions which causes failure of protein digestion

232
Q

What are possible causes of hypochlorhydria?

A

Age, stress, medications, bacterial infection, zinc deficiency, or surgical procedures like gastric bypass

233
Q

Give symptoms of hypochlorhydria

A 
Presence of undigested food in stool
Flatulence
Bloating
Diarrhoea
Heartburn
Hair loss
Nausea
Nutrient deficiencies
234
Q

How can hypochlorhyria be treated?

A

Antibiotics for H. pylori infection or a change to current medications.

235
Q

What factors increase HCl secretion?

A

Histamine, ACh, gastrin, caffeine, alcohol, NSAIDs, nicotine, H. pylori, Zollinger-Ellison syndrome, hyperparathyroidism and stress

236
Q

What cells secrete pepsin?

A

Chief cells secrete pepsin in the form of pepsinogen, an inactive zymogen

237
Q

How does acidity activate pepsinogen?

A

Shape is altered by high acidity, which exposes its active site in an autocatalytic feedback process

238
Q

What stimulates pepsinogen secretion?

A

Nerve inputs to chief cells

239
Q

How do NSAIDs cause topical irritation to the gut?

A

They impair the barrier properties of the mucosa and suppress gastric prostaglandin synthesis. They decrease gastric mucosal flow, interfere with repair of superficial injury and inhibit platelet aggregation.

240
Q

How does the liver contribute to lowering blood glucose levels?

A

By regulating the flux into the pathways that remove free glucose

241
Q

Name 2 serum proteins of which the liver is the major site of synthesis?

A

Albumin and clotting factors

242
Q

What does the liver convert glucogenic amino acids to?

A

Sugars

243
Q

What does the liver convert ketogenic amino acids to?

A

Ketone bodies

244
Q

What processes is the liver the major site for regarding amino acid metabolism and urea metabolism?

A

Transamination and deamination of amino acids.

Detoxification of ammonia

245
Q

What 3 processes involving lipids does the liver play a central role in?

A

Synthesis, transport and metabolism

246
Q

What percentage of endogenous cholesterol does the liver make?

A

Around 50%

247
Q

What is cholesterol made from?

A

Acetyl CoA

248
Q

What is the key enzyme to cholesterol synthesis?

A

HMG-CoA reductase

249
Q

What’s cholesterol transported from the liver as?

A

VLDL

250
Q

What system disposes of cholesterol?

A

The biliary system

251
Q

What are the 2 routes to the metabolism of ethanol by the liver?

A

Oxidation through the activity of alcohol dehydrogenase (80-90%)
Microsomal oxidation using cytochrome P450 (10-20%)

252
Q

What is the first reaction in the metabolism of ethanol?

A

The conversion of ethanol to acetaldehyde in a process requiring alcohol dehydrogenase and NAD+, which gets protonated

253
Q

What mass of alcohol is metabolised per hour?

A

Around 10g

254
Q

What is methanol metabolised to?

A

Formaldehyde

This is very toxic and associated with blindness, paralysis and loss of consciousness

255
Q

What is the second reaction in metabolism of ethanol, once it’s become acetaldehyde?

A

Conversion of acetaldehyde to acetate, which requires aldehyde dehydrogenase and NAD+ + H2O, which forms NADH and 2H+

256
Q

Caucasians have 2 isoforms of acetaldehyde dehydrogenase. What are they?

A

ALDH-1 and ALDH-2

257
Q

What is the main isoform of acetaldehyde dehydrogenase?

A

ALDH-2, which is mitochondrial with a low km

258
Q

Around 40% of east-asians are intolerant to ethanol. What are the symptoms?

A

Vasodilation, facial flush, tachycardia and nausea

259
Q

What converts acetate to acetyl CoA?

A

Acetyl CoA synthase

260
Q

Why are large quantities of acetyl CoA, NADH and ATP formed from alcohol?

A

Oxidation of alcohol takes precedence over other nutrients and there’s no negative feedback for its metabolism

261
Q

How do acetyl CoA, NADH and ATP formed from alcohol metabolism affect glucose metabolism?

A

They inhibit glucose metabolism by inhibiting PFK and pyruvate dehydrogenase

262
Q

How do NADH and acetyl CoA affect the TCA cycle?

A

NADH inhibits the cycle, and acetyl CoA inhibits it further

263
Q

What does acetyl CoA production from alcohol lead to?

A

Ketone body formation and the stimulation of fatty acid synthesis. Fatty acids are esterified to TG for export as VLDL

264
Q

What is the second route of ethanol metabolism?

A

The microsomal ethanol-oxidising system

265
Q

What does the microsomal ethanol-oxidising system involve?

A

The oxidation of ethanol by members of the cytochrome P450 family of enzymes, using NADPH, which is required for the synthesis of the antioxidant glutathione

266
Q

What highly reactive substance can accumulate with excessive ethanol intake?

A

Acetaldehyde

267
Q

How can acetaldehyde accumulation affect the body?

A

Acetaldehyde can inhibit enzyme function. In the liver, this can lead to reduction in the secretion of both serum protein and VLDL. It can also enhance free-radical production, leading to tissue damage such as inflammation and necrosis

268
Q

What are the 3 stages of alcohol liver damage?

A

Stage 1- fatty liver
Stage 2- alcoholic hepatitis (groups of cells die, resulting in inflammation)
Stage 3- cirrhosis, which includes fibrosis, scarring and cell death

269
Q

What happens in a cirrhotic liver?

A

Ammonia accumulates, resulting in neurotoxicity, coma and possibly death.

270
Q

What proportion of cirrhosis is due to alcohol?

A

75% of cases

271
Q

What proportion of alcoholics get cirrhosis?

A

Around 25%

272
Q

What are xenobiotics?

A

Compounds not naturally produced in the body that have no nutritional value

273
Q

Name some xenobiotics

A

Plant metabolites, synthetic compounds, food additives, agrochemicals, cosmetics, drugs

274
Q

The liver plays a major role in xenobiotic metabolism. What’s its aim?

A

To make xenobiotics harmless and more readily disposed of by the kidney in urine or the gut in faeces

275
Q

What are the 3 phases of metabolism of xenobiotics?

A

Phase 1- oxidation
Phase 2- conjugation
Phase 3- elimination

276
Q

What other modifications of xenobiotics are possible besides oxidation?

A

Hydroxylation and reduction

277
Q

What is the point of the modification in phase 1?

A

To increase solubility of the xenobiotic by introducing functional groups that enable participation in further reactions promoted by cytochrome P450

278
Q

Where is cytochrome P450 mostly found?

A

In the liver and cells of the intestine

279
Q

What happens in conjugation of xenobiotics (phase 2)?

A

Xenobiotics are modified by addition of groups such as glutathione, glucuronic acid and sulphate to increase solubility and target the xenobiotics for excretion

280
Q

Why is xenobiotic metabolism a potential clinical hinderance?

A

The body does’t distinguish between harmful compounds and beneficial compounds such as therapeutic drugs. Oral drugs pass through the liver first, and modification made can significantly reduce the effectiveness of the drug

281
Q

How do statins work?

A

Statins inhibit HMG-CoA reductase, which is crucial to cholesterol biosynthesis

282
Q

What degrades statins?

A

CYP3A4, which can be inhibited by components of grapefruit juice

283
Q

What is aflatoxin B1?

A

A very potent carcinogen produced by the fungus Aspergilus flavus, which is activated bt P450 isoenzymes, leading to epoxide formation and hepatocarcinogenesis

284
Q

How does the liver metabolise paracetamol?

A

The liver first conjugates it with glucoronate to produce a soluble molecule that’s readily excreted by the kidney, or sulphated for similar effects. There is a small amount of metabolism by P450 to form NADPQL, which is metabolised with the aid of glutathione to form a soluble molecule excreted in urine

285
Q

What is the mechanism of peptic ulcer formation?

A

Breakage of the mucosal barrier- imbalance between protective and damaging factors. Then tissues are exposed to the erosive effects of HCl and pepsin, leading to ulcers

286
Q

Where are the 3 commonly affected sites for ulcers?

A

The oesophagus, stomach and duodenum

287
Q

Name 7 factors that prevent infection of the gastric mucosa?

A 
HCl
Peyer's patches
Mucus production
IgA secretion at mucosal surfaces
Peristalsis and fluid movement
Fast cell turnover
Seamless epithelium with tight junctions
288
Q

What protective factors prevent auto digestion of the stomach?

A

Secretion of alkaline mucus and HCO3-
Protein content in food
Presence of tight junctions between epithelial cells and the fibrin coat
Replacement of damaged cells within the gastric pits
Prostaglandins inhibit acid secretion and enhance blood flow

289
Q

Describe H. pylori

A

Gram-negative, aerobic spirochete bacteria that can be coccoid

290
Q

Describe how H. pylori infects the gut

A

H. pylori penetrates the gastric mucosa via flagella that enable ‘corkscrew motility’ towards the gut epithelium

291
Q

What are 5 virulence factors of H. pylori?

A

Motility- it moves closer to the epithelium where pH is favourable
Uses mucinase activity to digest the protective mucus layer
Produces urease to form ammonia that buffers gastric acid
Cytotoxin-associated antigen (CagA) inserts pathogenicity islands and confers ulcer-forming potential
Vacuolating toxin A (VacA) alters the trafficking of intracellular protein in gastric cells

292
Q

What does H. pylori infection positively dysregulate?

A

Gastrin secretion

293
Q

What is the basic description of the cause of peptic ulcers?

A

Increase gastric acid secretions that lead to mucosal breakdown

294
Q

Name aggravators of peptic ulcers

A

Regurgitated bile acids, NSAIDs, genetics, smoking, alcohol, spicy food, chronic gastritis and H. pylori infection

295
Q

What does mucinase released from H. pylori do?

A

Breaks down the protective alkaline mucus layer of the gut

296
Q

What does urease released from H. pylori do?

A

Urease converts urea to ammonia, which buffers gastric acid and produces CO2

297
Q

What 4 specific locations are common sites of peptic ulcers?

A

The first part of the duodenal cap
The junction of the body and antrum of the stomach
The distal oesophagus, especially in Barrett’s oesophagus
Meckel’s diverticulum in the small intestine

298
Q

What are 2 options for diagnostic tests for a suspected peptic ulcer?

A

Endoscopy (oesophagogastroduodenoscopy)

Histological examination and staining of an EGD biopsy

299
Q

What are 2 tests for the presence of H pylori?

A

Stool antigen test

Evaluation of urease activity via a urea breath test

300
Q

What are symptoms of a peptic ulcer?

A

Anaemia, black, tarry stools, nausea, dyspepsia, anorexia, vomiting, haematemesis, epigastric pain, chest discomfort, weight loss

301
Q

Where does chronic peptic ulcer occur?

A

The upper GIT

302
Q

Name 5 complications of peptic ulcers

A

Haemorrhage
Perforation (peritonitis)
Penetration, which may lead to leakage of luminal contents
Narrowing of the pyloric canal or oesophageal stricture
Malignant changes (3-6 times more likely with H. pylori infections)

303
Q

Name 4 H2 receptor antagonists

A

Cimetidine, ranitidine, famotidine and nizartidine

304
Q

What is the clinical use of H2 receptor antagonists?

A

Treatment of peptic ulcers and reflex oesophagitis

305
Q

How do H2 receptor antagonists work?

A

They inhibit histamine action on parietal cells, reducing gastric acid secretion and pepsin secretion. They can decrease basal and food-stimulated acid secretion by around 90%

306
Q

What are the side effects of H2 receptor antagonists (although rare)?

A

Diarrhoea, muscle cramps, hypergastrinaemia and transient rashes

307
Q

What can cimetidine rarely cause in men?

A

Gynaecomastia, which decreases sexual function

308
Q

How does cimetidine affect drug metabolism?

A

Cimetidine inhibits P450 enzymes, which decreases metabolism of anticoagulants and tricyclic antidepressants like imipramine, dosulepin and amitriptyline

309
Q

Which drug has a lower IC50, ranitidine or cimetidine?

A

Ranitidine

310
Q

Name 4 proton pump inibitors

A

Omeprazole, lansoprazole, pantoprazole and rabeprazole

311
Q

What are the (3) clinical uses of proton pump inhibitors?

A

Treatment of peptic ulcers and reflux oesophagitis and of Zollinger-Ellison syndrome

312
Q

What is the mechanism of action of proton pump inhibitors?

A

They are weka bases that are inactive at neutral pH and irreversibly inhibit the K+ H+ ATPase pump. They decrease basal and food-stimulated gastric acid secretion

313
Q

What are the side-effects of proton pump inhibitors?

A

Headache, diarrhoea, mental confusion, rashes, somnolence, impotence, gynaecomastia and dizziness

314
Q

What drugs are gastroprotective?

A

Prostaglandins (PGE2 and PGI1)

315
Q

What is misoprostol?

A

A stable analogue of PGE1 that works by inhibiting basal and food-stimulated gastric acid secretion and inhibiting histamine- and caffeine-induced gastric acid secretion. It increases mucosal blood flow and can augment the secretion of HCO3- and mucus

316
Q

What are pancreatic acini?

A

Clusters of cells that produce digestive enzymes and secretions and make up the bulk of the pancreas

317
Q

What is meant by ‘the pancreas is a dual organ’?

A

It has exocrine and endocrine portions

318
Q

What do acing cells contain?

A

Zymogen granules

319
Q

What are acing cells surrounded by?

A

A basal lamina

320
Q

What cells form an intercalated duct?

A

Centroacinar cells

321
Q

What part of the pancreas do acini form?

A

The exocrine part, as they secrete digestive enzymes

322
Q

What extend from the apical side of acinar cells?

A

Microvilli

323
Q

How much fluid does the exocrine pancreas secrete per day?

A

1.5L

324
Q

What does the pancreas secrete?

A

HCO3- and sodium-rich juice containing albumin, globulin and digestive enzymes

325
Q

What is significant about the enzymes secreted in pancreatic juice?

A

They are inactive forms to prevent auto digestion, and they activate in the duodenum at the brush border

326
Q

How is composition of pancreatic juice modified as it travels through the duct?

A

Cl- is actively exchanged for HCO3- by the epithelial cells. H+ is actively eliminated, so more CO2 and HCO3- is produced in blood. H+ is exchanged for K+ and Na+, and neutralises HCO3- to form H2CO3. CO2 diffuses in and forms H2CO3 with H2O

327
Q

What 3 major types of enzymes does the pancreas secrete?

A

Proteolytic enzymes
Amylase
Lipase

328
Q

What are the 3 proteolytic enzymes secreted by the pancreas?

A

Trypsin, chymotrypsin and carboxypeptidase

329
Q

What’s trypsin secreted by the pancreas as?

A

Trypsinogen, which is activated by enteropeptidase and by trypsin itself

330
Q

What activates pancreatic alpha-amylase?

A

Cl-

331
Q

What activates elastase?

A

Trypsin activates elastase to digest elastin

332
Q

What activates phospholipase A2?

A

Trypsin activates phospholipase A2 to digest phospholipids

333
Q

What are chymotrypsins secreted sand what do they do?

A

Chymotrypsin is secreted as chymotrypsinogen and activated by trypsin to digest proteins and polypeptides

334
Q

What do carboxypeptidase A and B digest?

A

They’re activated by trypsin to digest proteins and polypeptides

335
Q

What causes enterokinase secretion?

A

CCK

336
Q

Whta is enterokinase?

A

A brush border enzyme that converts trypsinogen to trypsin.

337
Q

What are Kazal inhibitor, enzyme Y, chymotrypsin C and caldecrin?

A

Autodigestion inhibitors

338
Q

What happens in acute pancreatitis?

A

Trypsin activates phospholipase A2 in the pancreatic duct. PLA2 converts lecithin to isolecithin. Isolecithin disrupts pancreatic tissue, causing membrane damage and necrosis

339
Q

What are symptoms of pancreatic lipase insufficiency?

A

Malabsorption and steatorrhea

340
Q

What are the 4 mediators of pancreatic secretions?

A

Neurocrine signals
Vagal parasympathetic stimulation (enhances rate of secretion)
Sympathetic stimulation (inhibits secretion)
Secretin and CCK stimulate secretion

341
Q

What happens in the cephalic phase involving the pancreas?

A

Vagal stimulation of gastrin release from the antrum via ACh and VIP leads to secretion of some protein-rich pancreatic juice

342
Q

What happens in the gastric phase regarding pancreatic secretions?

A

Distension and the vagal reflex on the fundus or antrum, and amino aicd- and peptide-stimulated gastrin secretion leads to release of enzyme-rich pancreatic juice

343
Q

What happens in the intestinal phase with regards to pancreatic secretions?

A

Chyme in the duodenum and jejunum induces secretion of pancreatic juice via CCK and secretin

344
Q

What effect does secretin from the duodenum and jejunum have on the pancreas?

A

Secretin acts at duct cells to induce HCO3- rich pancreatic juice secretion

345
Q

What effect does CCK from the duodenum and jejunum have on the pancreas?

A

CCK stimulates pancreatic acing cells to synthesis and release enzyme-rich pancreatic juice. CCK also potentiates the effects of secretin

346
Q

What does cystic fibrosis affect?

A

The sinuses, lungs, skin, liver, pancreas, intestines and reproductive organs. It can block the pancreatic ducts

347
Q

What’s the direct pathway of gastric acid secretion?

A

ACh, gastrin and histamine all stimulate the parietal cells and trigger secretion of H+ into the lumen

348
Q

Where in the GIT is gastrin secreted?

A

The gastric mucosa and duodenum

349
Q

What effects do milk and Ca2+ have on gastrin secretion?

A

They stimulate gastrin release

350
Q

What effects does metoclopramide have on gastric motility and emptying?

A

Metoclopramide inhibits pre- and post-synaptic dopamine receptors (D2) as well as 5-HT3 receptors in the CNS to inhibit vomiting. It stimulates various 5-HT receptors in the ENS for pro kinetic effects, and also stimulates inhibitory nitrergic neurons for coordinated gastric motility

351
Q

How does dopamine affect the gut?

A

Dopamine inhibits release of ACh from intrinsic myenteric cholinergic neurons by activating prejunctional D2 receptors. Dopamine has relaxant effects on the LOS and fundus and antrum by activating D2 receptors. Dopamine can induce contraction in the proximal intestine but relaxation in the distal intestines

352
Q

What type of drug is metoclopramide?

A

A D2 receptor antagonist

353
Q

How does metoclopramide affect gastric motility?

A

It increases release of ACh and increases intragastric pressure by increasing LOS tone and tone of gastric contractions. These improve antroduodenal coordination, which accelerates gastric emptying and relaxes the pyloric sphincter

354
Q

Through additional pro kinetic effects, how does metoclopramide cause coordinated gastric motility?

A

Metoclopramide stimulates presynaptic excitatory 5-HT receptors and inhibitory nitrergic neurons

355
Q

How does metoclopramide elicit antiemetic effects?

A

Metoclopramide inhibits central pre- and post-synaptic D2 receptors and 5-HT receptors to inhibit vomiting

356
Q

What is metoclopramide used for? (5)

A 
Symptoms of gastroparesis
Promotes gastric emptying
Anti-emetic effects via CNS
GORD
Nausea due to surgery ir cancer
357
Q

What is metoclopramide useless for?

A

Paralytic ileus, because it causes moderate to diffuse abdominal discomfort

358
Q

Which serotonin receptors does metoclopramide stimulate?

A

5-HT4

359
Q

What do antispasmodic agents do?

A

Decrease spasm in the bowel by relaxing smooth muscle.

360
Q

What type of drug is propantheline?

A

An antimuscarinic agent (inhibits parasympathetic activity)

361
Q

What is propantheline used for?

A

Irritable bowel syndrome and diverticular disease

362
Q

What are the goals of pharmacological intervention in gastric ulcers? (3)

A

Reduce acid secretion with H2 receptor antagonists
Neutralise secreted acid with antacids
Attempt to eradicate H. pylori

363
Q

What’s the general mechanism of action of antacids?

A

Neutralise the acid

Increase the pH of gastric acid, as peptic activity stops at pH 5

364
Q

Name an antacid with cytoprotective effects

A

Bismuth chelate

365
Q

How does bismuth chelate work?

A

It protects the gastric mucosa by forming a coat over the crater of the ulcer, absorbing pepsin and increasing HCO3- and PG secretion

366
Q

What are signs of bismuth chelate use?

A

It blackens the stool and the tongue. It can cause nausea and vomiting

367
Q

How can NSAIDs cause gastric bleeding?

A

They inhibit PG synthesis

368
Q

Name 2 selective COX-2 inhibitors that decrease gastric bleeding

A

Celecoxib and rofecoxib

369
Q

How does bismuth chelate affect H. pylori?

A

It has toxic effects, preventing the adherence of H. pylori to the mucosa or inhibiting its proteolytic activity

370
Q

What may happen to plasma bismuth chelate concentration in someone with renal impairment?

A

Plasma bismuth chelate concentration may rise dangerously high and cause encephalopathy

371
Q

What can’t you do if you’re taking metronidazole for H. pylori infection?

A

Drink alcohol, as disulfiram-like reactions result

372
Q

Why can’t you drink alcohol while taking metronidazole for H. pylori infection?

A

Disulfiram inhibits acetaldehyde dehydrogenase, leading to acetaldehyde build-up and unpleasant flushing and nausea

373
Q

What are consequences of constipation as a result of rectal distension?

A

Headache, loss of appetite, nausea and abdominal distension and pain

374
Q

What does holding of faecal matter lead to?

A

Increased water loss and drier faeces, leading to more painful, difficult defecation

375
Q

What causes constipation?

A

Diet, or decreased motility of the large intestine due to age, disease, drugs or enteric NS damage

376
Q

What are alarm signs in patients with constipation?

A 
Acute onset constipation in elderly patients
Weight loss >10lb
Haematochezia
Anaemia
Family history of colon cancer or IBD
377
Q

What are possible causes of haematochezia?

A

Diverticular disease, anal fissure, colitis, angiodysplasia, peptic ulcers, polyps and colorectal cancer

378
Q

How do purgatives like laxatives, faecal softeners and stimulant purgatives help constipation?

A

They retain water in the gut lumen to promote peristalsis

379
Q

How does lactulose, a laxative work?

A

It reaches the colon unchanged. Here, bacteria break it down into short-chain fatty acids. Osmotic pressure and biomass increase, leading to softening of the faeces and increased stool volume. Peristalsis is stimulated and colonic transit time is shortened

380
Q

What causes diarrhoea?

A

Infectious agents, toxins, anxiety, and drugs like amitryptiline, doxepin, clonidine, codeine, tramadol and methadone

381
Q

What are the therapeutic strategies to diarrhoea treatment?

A

Maintain fluid and electrolyte balance via oral rehydration therapy. Use anti-infectives. Use anti-motility drugs- adsorbents that modify fluid and electrolyte transport

382
Q

What is the main cause of gastroenteritis?

A

Campylobaceter sp

383
Q

What is loperamide (Imodium)?

A

An anti-diarrhoea medication that can treat diarrhoea or IBS. It’s also used for longer lasting diarrhoea from bowel problems like Crohn’s disease, ulcerative colitis and short bowel syndrome

384
Q

What’s the mechanism of action of loperamide?

A

Loperamide is an opioid receptor agonist that exerts its effects on the µ-opioid receptor of the myenteric plexus of the large intestine, inhibiting gastric emptying by increasing sphincter tone. This induces stationary motor patterns and blocks peristalsis

385
Q

Does loperamide have central effects?

A

No, as it doesn’t cross the BBB

386
Q

What’s the daily fluid intake breakdown in the average adult?

A

2550ml
Liquids: 1200ml
Food: 100ml
Metabolically produced: 350ml

387
Q

What’s the daily fluid output breakdown in the average adult?

A 
2550ml
Insensible loss via skin and lungs: 900ml
Sweat: 50ml
Faeces: 100ml
Urine: 1500ml
388
Q

What’s the daily NaCl intake in an average adult?

A

10.5g

389
Q

What classifies as diarrhoea (frequency-wise)?

A

> 3 unformed stools per 24 hour period

390
Q

What are 3 causes of decreased absorption of water and the type of diarrhoea that accompany them?

A

Increased number of osmotic particles (osmotic diarrhoea)
Increased rate of flow of intestinal contents (deranged motility diarrhoea)
Abnormal increase in secretion of the GIT (secretory diarrhoea)

391
Q

What 2 situations cause osmotic diarrhoea?

A

1) Ingestion of poorly absorbed substrate- usually a carbohydrate or divalent ion (mannitol, sorbitol, Epson salt, antacid)
2) Malabsorption- inability to absorb certain carbohydrates most commonly. (A common cause example is lactose intolerance)
These situation cause decreased absorption of electrolytes and nutrients

392
Q

How does lactose intolerance work?

A

A moderate quantity of lactose is consumed, but the intestinal epithelium is deficient in lactase, and lactose cannot be effectively hydrolysed into glucose and galactose for absorption. Osmotically-active lactose is retained in the intestinal lumen, where it ‘holds’ water. Lactose passes into the large intestine and is fermented by colonic bacteria, resulting in excessive flatulence

393
Q

When does osmotic diarrhoea stop?

A

When the patient fasts or stops consuming the poorly absorbed solute

394
Q

How does secretory diarrhoea work?

A

ACh, substance P and neurotensin act via increased Ca2+ concentration to increase rate of intestinal secretions. Diarrhoea occurs when secretion of water into the intestinal lumen exceeds absorption

395
Q

What can cause uncontrolled water secretion from crypt enterocytes?

A

Bacterial toxins that strongly activate adenylate cyclase, causing a prolonged increase in intracellular [cAMP] within crypt enterocytes. This results in prolonged opening of Cl- channels

396
Q

Besides bacterial toxins, what other agents can cause secretory diarrhoea?

A

Some laxatives, hormones (e.g. VIP) secreted by certain tumours, certain drugs, or certain meals, organic toxins and plant products

397
Q

What diarrhoea does IBD cause?

A

Chronic exudative diarrhoea

398
Q

How does deranged motility diarrhoea occur?

A

Lack of absorption, so some agents may promote secretion as well as motility.

399
Q

How may GI stasis promote diarrhoea?

A

It may stimulate bacterial overgrowth

400
Q

Name 2 parasites that cause diarrhoea

A

Entamoeba histolytica and Giardia lamblia

401
Q

Describe entamoeba histolytica infection

A

It can be asymptomatic or cause amoebic dysentry. Onset is gradual and gives systemic symptoms like anorexia and headaches

402
Q

Describe Giardia lamblia infection

A

Causes steatorrhoea and abdominal pain. Causes maldigestion and malabsorption of lipids, CHOs, vitamin A and B12, and folic acid

403
Q

What 3 causes are there for bloody diarrhoea?

A

Chronic disease
Ulcerative colitis
Neoplasm

404
Q

What are the 2 major consequences of severe diarrhoea?

A

Hypovolaemia

Metabolic acidosis due to loss of HCO3-

405
Q

Briefly describe vomiting

A

Retrograde giant contractions that lead to oral expulsion of the upper GI contents and bile

406
Q

What sympathetic effects occur from vomiting?

A

Sweating, salivation and heart rate incresae

407
Q

What controls vomiting?

A

The central trigger zone in the area postrema of the medulla oblongata in the brainstem

408
Q

What inputs can initiate vomiting?

A

Distension of the stomach or small intestine
Action of some substances on chemoreceptors in the brain or intestines
Increased intracranial pressure
Motion sickness
Intense pain
Tactile stimulus to the back of the throat
Sight, smell and emotional circumstances

409
Q

What are the consequences of excessive vomiting?

A 
Increased salt and water loss
Severe dehydration
Circulatory problems (hypovolaemia)
Metabolic alkalosis due to loss of H+
Nutritional deficit and failure to thrive
Death
410
Q

What is lost in vomit?

A

Food, mucus with Na+, K+, Cl- and HCO3-, gastric acid, upper GI contents e.g. bile, and possibly blood

411
Q

What are the consequences of fluid loss form the GI tract?

A 
Hypovolaemia
Haemoconcentration/ polycythaemia
Dehydration
Ionic imbalance and poor perfusion of tissues
Malnutrition and increased mortality
412
Q

What are the circulatory consequences of hypovolaemia?

A 
Decreased venous return
Arterial hypotension
Myocardial dysfunction
Increased anaerobic metabolism and acidosis
Multi-Organ failure
413
Q

What are symptoms of dehydration?

A 
Nausea
Headache
Irrationality
Cramps
Increased temperature
Dizziness
Decreased skin turgor
Heat shock
Fainting
Blood clotting
Constipation
Acid reflux
Indigestion
414
Q

How does the body respond to water loss?

A

Cardiovascular adaptation and renal adaptation

415
Q

What’s the renal adaptation to profuse sweating?

A

Hypoosmotic salt solution is lost, so plasma volume decreases. This stimulates increase in GFR and plasma aldosterone, both of which decrease Na+ excretion. Increase in plasma osmolarity from water loss increases plasma vasopressin to decrease H2O excretion

416
Q

What happens when the macula dense senses low NaCl concentration?

A

Renin release is increased and resistance to blood flow in the afferent arterioles is decreased by vasodilation

417
Q

How does ADH work?

A

ADH inserts aquaporin-2 channels into the membrane of the collecting duct of the kidney, which increases the permeability of the collecting ducts to H2O, resulting in concentrated urine of low volume

418
Q

What factors regulate ADH release?

A 
Large decrease in blood volume detected by baroreceptors
Severe dehydration
Intake of copious amounts of water
Hyperventilation
Vomiting/ diarrhoea
Fever, heavy sweating or burns
419
Q

What’s the problem with diarrhoea-induced hypercalcaemia?

A

It gives increased risk of kidney stones, kidney failure and arrhythmia. Symptoms include nausea, vomiting, loss of appetite, constipation, abdominal pain, excessive thirst, fatigue, muscle weakness and joint pain

GUT Year 1 (2 decks)

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