Case 1 Flashcards
1
Q
What are some dysfunctional physiologies and disease of the mouth?
A
- Oral ulceration: break in the oral epithelium, exposing nerve endings in underlying connective tissue
- Stomatisis: inflammation of the lining of any of the soft tissues of the mouth
- Leukoplakia (painless white patches in the side of the tongue/ cheek
- Dysphagia (difficulty swallowing)
- Mumps: infection of the salivary gland - can cause sterilisation in men
2
Q
What are some causes of oral ulceration?
A
- Physical or chemical injury
- Drugs
- Malignancy
- Systematic diseases
3
Q
What are some causes of stomatitis?
A
- Poor hygiene
- Poorly fitter dentures
- Heat burns
- Drugs
- Allergy
- Infections
4
Q
Dysfunctional physiologies and disease of the oesophagus
A
- GORD - can lead to Barrett’s oesophagus
- Hiatal hernia
- Motiloty disorders
- Achalasia - inadéquat LOS relaxation
- Diffuse oesophageal spasm - uncoordinated contraction
- Hypercontraction
- Ineffectice oesophageal motility - hypocontraction
5
Q
Causes of GORD
A
- Meds
- Obesity
- Spicy and acidic food
- Smoking
6
Q
What can GORD lead to?
A
Barrette’s oesophagus
7
Q
What is a hiatal hernia?
A
When part of the stomach pokes up and gets stuck in the diaphragm - high risk of infection -> need surgery
8
Q
What are the motility disorders of the oesophagus?
A
- all muscular disorders
- achalasia: inadequate LOS relaxation
- diffuse oesophageal spasm - uncoordinated contraction
- hyper contraction
- ineffective oesophageal motility- hypo contraction
9
Q
What does GORD do?
A
- Causes exposure of ‘unprotected’ oesophageal squamous epithelium to acid
- Have transient LOS relaxation in absence of swallowing - response of stimulation of gastric vagal mechanoreceptors and oesophageal hypomotility
10
Q
What are the three types of dyspepsia and GORD?
A
- non-erosive reflux disease (heart burn)
- erosive oesophagitis (acute inflammatory response)
- barrettes oesophagus (metaplasia of mucos) => cancer risk
11
Q
What are the three acid secretion pathways?
A
- Ach (M3 receptor)
- Histamine (H2 receptor)
- Gastrin (CKKB/CCK2 receptor) => directly and indirectly indue HCl secretion
12
Q
What is the most powerful stimulus for HCl secretion?
A
Histamine which acts through G-coupled receptor to increase cAMP
13
Q
How do prostaglandins regulate acid production?
A
- PGE2 is produced by COX2/1 and increases mucus production
14
Q
How do NSAIDs prevent mucus being produced?
A
- Binds to COX1/2 and prevents PGE2 being produced
- acidic so can cause gastric ulcers
15
Q
How can prominent stress cause peptic ulcers?
A
Inhibit HCO3- production
16
Q
How does mucus protect the stomach from HCl?
A
- Trapping HCO3- rich fluid near apical border of epithelia
- HCO3- stops acid damage
- The apical cell membrane TJ limits H+ ion diffusion and locally produces PGE2 and PGI2 which increases mucus production and decreases HCl
17
Q
Who does peptic ulcer disease affect?
A
All ages but rare in children
18
Q
What are the two types of peptic ulcers?
A
- Gastric
- Duodenal
19
Q
Who do gastric ulcers typically present in?
A
55-65 yrs old
20
Q
Who do duodenal ulcers typically present in?
A
25-75 yrs old
21
Q
If peptic ulcers are presenting in >45yr olds, what does that mean?
A
Possibly cancerous => investigate further
22
Q
Who’s more at risk of getting peptic ulcers?
A
- Males are more at risk
- Females are more likely to get gastric rather than duodenal
23
Q
What sort of genetic factors contributed to peptic ulcers?
A
- increased acid production
- weaker mucosa
- abnormal mucus production
24
Q
What causes peptic ulcers?
A
- stress
- H.pylori
- long term NSAID use
- caffeine and smoking
25
Which ulcer is made worse with food?
Gastric ulcers - associated with weight loss, anorexia and nausea
26
Which ulcers are made worse at night?
Duodenal as gastric juice may enter and the pH is lower due to no food and lying down
27
What is the pathophysiology of gastric ulcer?
- Normally an inflammatory response of parietal cells - atrophic gastritis (less able to secrete acid and increase pH)
- normal/ decreased acid secretion
28
What is the pathophysiology of duodenal ulcers?
- Associated with an increase in H+ (due to increase gastrin) and decreased HCO3-
- Gastric inflammation elevated in pyloric region
29
What is the pathophysiology of H.pylori?
- Infects the lower part of the stomach and causes inflammation of the gastric mucosa
- May lead to an ulcer, proliferation and bleeding
30
How do NSAIDs cause peptic ulcers?
- Reduce prostaglandin formation (COX1 inhibition) and may trigger gastric ulceration and bleeding which decreases HCO3- => decreasing mucus production and blood flow
- Aspirin causes irreversible inhibition
31
What are three neutralisation methods for gastric acid?
- Antacids
- Alginates
- Sucralfate (mucosal protectants)
32
How to reduce acid secretion?
- PPI
- Histamine H2 receptor antagonists
33
What helps move things faster?
Prokinetics
34
What are antacids?
Formed from weak bases (mainly weak inorganic bases) and neutralise excess acid in the stomach and reduce foaming => prevents heartburn
35
What are antacids often combined with?
Alginates and anti foaming agents => decrease surface tension which prevents bubbles as they’re trapped in an egg box
36
Pros and cons of systematic antacids
- Useful in short term therapy - rapid onset of action
- Prolonged use can cause overload on the kidneys
37
Pros of non systematic antacids
- Most of them remain in the GIT
- Examples: Tums (Ca), milk of magnesia (Mg)
38
Disadvantage of antacids
-Binding of other drugs can cause reduced bioavailability and chemical inactivity
- Mg - laxative properties - not in renal failure
- Al - constipation
- Calcium carbonate- kidney stone?/ constipation
- Carbonates - generate CO2=> bloating and flatulence
- NaHCO3 - problems with hypertension and renal insufficiency and metabolic acidosis
39
What are alginates?
Polysaccharides found in the cell walls of brown algae and it forms a protective barrier on top of gastric contents (usual combine with antacids)
40
What is gavicson?
- Combination of antacids and alginates
- reacts rapidly with acid to form a raft (egg box) of alginic-acid gel (pH~7) => floats on the stomach contents => impending gastro-oesophageal reflux
41
How do PPI work?
- Bind to parietal cells (specific H+/k+ ATPase) so they inhibit HCl production as proton pump can’t move to the surface
- prodrugs - activated in strongly acidic conditions
- activated form irreversibly binds to cystein of the H+/K+ ATPase to inhibit the active proton pump
42
What are the different ways that histamine is released in the stomach?
- H2 receptors (expressed by parietal cells)
- ECL cells (gastrin stimulation)
- Mast cells (during infection)
43
How is the PPI activated?
Activated by proton-catalysed (pH~5) formation of sulfonic acid and the drug irreversibly binds to sulphydryl groups of cysteines of H+/K+ ATPase
44
Examples of H2 receptor blockers
- Cimetidine (inhibits P450)
- Ranitidine (doesn’t inhibit P450=> fewer side effects)
45
Mechanism of action of histamine receptor blockers
Acts as a competitive antagonist of H2 receptors on the basolateral membrane of parietal cells. Completely block the histamine-mediated component of acid secretion and reduce secretions evoked by gastrin and acetulylcholine
Only effective for ~28 days
46
What reduces the effects of H2 blockers?
Smoking
47
How to prostaglandins reduce acid secretion?
- Bind to EP3 receptors on parietal cells
- Have cytoprotective effects which stimulate mucin and bicarbonate production
48
What is a synthetic analog of PGE1?
Misoprostol - inhibits basal and stimulated secretion of acid
49
What is sucralfate used for?
Used to treat begnign gastric and duodenal ulceration
50
Why are dopamine receptor antagonists used?
- Enhance prokinetics
- rarely used due to severe side effects
51
What is dyspepsia?
A collection of symptoms and typically presents as feeling pain/ discomfort located primarily in the upper abdominal region (not a diagnosis itself)
52
What can cause dyspepsia?
- Smoking
- Stress
- *H.pylori*
- Meds (NSAIDS)
- Diet
53
When should you investigate dyspepsia?
- Dysphagia is present (cancer?)
- Haematemosis
- >54 yrs old with weight loss
- Upper abdominal pain
- Reflux
54
How to test for H.pylori?
- Breath test
- Stool
- Blood
55
What should you do when testing for H.pylori?
Stop PPI use for two weeks (give antacids) and antibiotics for 4 weeks
56
What is the risk of triple therapy?
*C.difficile*
57
Issues with long term PPI use
- Rebound hypersecretion
- osteoporotic fractures
- Hypomagnesia
- Community and hospital acquired pneumonia
- Drug interactions?
58
How to investigate GORD?
Carry out an endoscope
59
What to prescribe for proven GORD?
- lifestyle advice
- full-dose PPI (4-8 weeks)
- severe? Full dose PPI
- recurring? Low dose (half dose) PPI
- refractory? Double dose and H2RA
60
Why would you give prokinetics to those with GORD?
Can increase LOS pressure and stimulate the motility (include metaclopromide => fairly toxic)
61
What is nausea?
An unpleasant sensation, vaguely referred to the epigastrium and abdomen with a tendency towards inward vomiting
62
What is vomiting?
Vomiting is involuntary contractions of the abdomen, thoracic and GI muscles so it is therefore forceful expulsions of stomach contents from the mouth
63
What is regurgitation?
The effortless return of oesophageal/ gastric contents in the mouth. It is unassociated with nausea or vomiting
64
What complications can nausea and vomiting cause?
- dehydration => tested by pinching someone’s skin
- electrolyte imbalances
- malnutrition
- aspirational pneumonia => when vomiting enters the lungs
- oesophageal tear
65
What is motion sickness?
When there is a disagreement in the brain between visually perceived movement and the vestibular systems sense of movement. Both acetylcholine and histamine are involved
Hyoscine butylbromide => anticholinergic
66
How to treat motion sickness?
Using anticholinergic drugs and antihistamines that cross the BBB
67
Side effects of anticholinergic
- drowsiness
- blurred vision
- dry mouth
- constipation
- urinary retention
- dementia => long term use as ACh is important for Brian’s development
68
What are the three different types of chemotherapy induced nausea and vomiting?
- acute - within 24hrs
- delayed - after 24 hours
- anticipatory - conditional response
69
What can affect CINV?
- type of chemo routine
- genotypic factors
- patient based factors - motion sickness: female/ morning sickness
70
What are the side effects of metoclopromide?
Helps with sickness but causes akathisia, tremors, dystonia, tardive dyskinesia (irreversible) => only given to >18 yrs
71
Examples of selective 5HT3 receptor antagonists in CINV
- ondasteron (pharmacogenetics in the future)
- palonesteon
72
Examples of neurokinin-1[NK1] receptor antagonists in CINV
Aprepitant
73
Example for corticosteroid for CINV
Dexamethasone
74
Example of D2 receptor antagonist in CINV
Metoclopromide
75
PONV risk factors
- female
- non-smoker
- post-operative opioids
- history of PONV or motion sickness
76
Complications of PONV
- increased hospital stay
- stress on surgical closure
- aspiration pneumonia
77
Management plan got PONV
1) zero risk factors: management is debatable => receive 0-2 antiemetics
2) one-two risk factors: give 2 antiemetics in combination
3) >2 risk factors: give 3-4 antiemetics in combination
78
What are the causes is NV in palliative care?
- chemicals
- gastric stasis
- bowel obstruction
- raised intracranial pressure
- psychological
79
What is rumination?
Food that is regurgitated in the postpranidal period, re-chewed and then re-swallowed
80
What are the consequences of coeliac disease?
- abdominal distension
- malabsorption
- diarrhoea
- anaemia
- intestinal cabcer
81
What is the cause of coeliac disease?
- Gluten is identified in the body by priming of IFNy, producing CD4+ cells by antigen peptides derived from alpha-gliadin (major protein in gluten). For immune recognition, alpha-gliadin must undergo deamination by tissues transglutaminase (tTG) => glutamine => glutamic acid
- has a genetic predisposition => major genes are on the human leukocytes antigen region (HLA) => highly polymorphic
82
What is IBD?
- Chronic inflammatory bowel diseases with features of autoimmune disease (Crohns and UC)
83
What does Crohns do?
- affects anywhere in the GIT
- causes thickening of the wall, cobblestoning, fishes (cracks) and fat wrapping
84
What does ulcerative colitis do?
- mainly affects the large intestines
- causes thinning of the vowel wall and pseudopolyps of the bowel
