The Patient - Semester 2 GI Flashcards
1
Q
How much small intestine in average human?
A
20m
2
Q
Path from mouth to rectum?
A
Mouth –> pharynx –> oesophagus –> stomach –> small intestine –> large intestine –> rectum
3
Q
What is mumps and where does it infect?
A
- Viral infections that involves salivary glands.
- It binds to receptors and cells in glands.
- Can also infect testes and make patient sterile.
- Can also infect pancreas.
4
Q
How does swallowing occur?
A
- Sensors in mouth and back of throat
- Relay info to brain which is fed to medulla oblongata
- Processed so impulses and action potentials fed back to throat allow swallowing.
5
Q
Two main nerves involved in swallowing process?
A
- Trigemirial
- Facial
6
Q
What is dysphagia?
A
Difficulty swallowing.
7
Q
What is the oesophagus hiates?
A
An opening in the diaphragm - there can sometimes be weakness at this point resulting hiatus hernia which can cause acid reflux.
8
Q
What is barrets oesophagus
A
- Usually lined with squamous epithelial cells under high power microscope
- Oesophagus and stomach are separated by the lower oesophageal sphincter –> a muscle sealing stomach and top and bottom
- This stops stomach acid from entering oesophagus.
- If stomach contents do move up epithelium - squamous cells are replaced by abdominal cells.
MAJOR ISSUE as cells replaced with are pre cancerous - these individuals are at higher risk of colenocarcinoma
9
Q
What is the purpose of mucous cells?
A
Act as a barrier across the surface of the stomach.
10
Q
What is the purpose of G cells?
A
Enteroendocrine secretes gastrin which stimulates acid production.
11
Q
What is the purpose of chief cells?
A
secrete pepsinogen/lipase
12
Q
What is the purpose of parietal cells?
A
(aka oxyntic cells) they secrete HCl
13
Q
What is pepsinogen?
A
- Pepsinogen is the inactive form of pepsin.
- When pepsinogen is exposed to acid it cleaves pepsinogen to pepsin (active)
- Now have enzyme to digest proteins.
14
Q
How is acid secreted into stomach?
A
1) Smell of food triggers receptors and stimulates stomach.
2) Binds to receptors on parietal cells and this causes release of H+ into lumen.
3) Gastrin released from G cells which binds to receptor on parietal cell and causes release of HCl
4) When you eat, stomach stretches causing a release of histamine. This binds to receptor on parietal cell again causing release of acid –> if we block this we can reduce release of acid.
15
Q
How do H2 receptor antagonists work?
A
Drugs bind to histamine receptor therefore less acid is released to lumen. e.g. Ametidine
16
Q
How do PPI’s work?
A
Example omeprazole.
- this irreversibly binds to proton pump and targets SH groups of pump to prevent acid being released.
- They prevent H+ release so only Cl- released fro, cell to lumen.
17
Q
How is self digestion prevented in the stomach?
A
1) Mucus foveolar cells –> secreted and its alkaline nature neutralises HCl
2) Tight junctions–> lock epithelial cells together. Restricts movement of the acid.
3) High cell turnover rate - damaged cells replaced
18
Q
What would happen if there was a breakdown in the mucus barrier?
A
- Epithelial cells would then be exposed to the HCl and pepsin –> this would then produce a gastric/duodenal ulcer.
- Duodenal = upper part of digestive system.
- Damage may extend deeper overtime into wall of GI tract (can result in haemorrhage or excessive bleeding)
19
Q
What is a perforated ulcer?
A
- Complete erosion through tract wall which allows contents of GI tract to move out and into peritoneal cavity (where intestines are held)
- This can lead to peritonitis and hospitalisation.
20
Q
What is a fatal consequence of peritonitis?
A
Sepsis.
21
Q
What is Helicobacter Pylori?
A
A flagellated bacteria which infects gastric mucosa. (leads to a decrease in barrier efficacy)
22
Q
What is the treatment for Helicobacter Pylori ?
A
2 antibiotics and a PPI.
Omeprazole, Carithromycin and Amoxicillin
or
Omperazole, Clarithromycin and metrondiazole
23
Q
What is the most proximal part of the small intestine called?
A
Duodenum.
24
Q
What is peristalsis?
A
Group of muscles called circular muscles and longitudal muscles contract which moves food down.
25
How is diarrhoea treated?
Reduce peristalsis activity so the faeces is exposed to epithelial cells for longer therefore more absorption occurs.
26
How is contraction controlled?
Controlled by nerves and neurones inside the MP (myenteric plexus)
27
Loperamide (Imodium) mechanism of action?
- Mechanism of action = binds to opioid receptors of the MP and reduces contraction of the muscles.
- However may cause constipation.
28
Purpose of bile acids?
- Emulsify lipids and allow their absorption.
| - Also needed for lipid soluble vitamins A, D, E, K which we need day to day.
29
Gastrointestinal adaptations:
1) Plicae (folds) - covered in finger like projections called villi which are also covered in microvilli.
2) epithelium = 1 cell thick
3) Enzymes- lots of them to convert non absorbable macromolecules to absorbable small molecules.
Glucose and galactose via sodium glucose transporter 1 SGLT 1
- Sodium Na+ dependent.
Fructose transported by GLUT5
30
How is protein digested?
- Proteins too large therefore chopped into small molecules.
- Small peptides transported by PEPT1 transporter (H+ dependent)
31
How are hydrophilic absorbed?
- Absorption via uptake transporters is extremely efficient
| - Hence why drugs are based on natural products e.g. peptide based drugs
32
Examples of PEPT1 substrates?
- Cephalosporins
- Penicillins
- Enalapril
- alphamethyldopaphenylalanine
- Valacyclovir
33
Examples of Organic Cation transporter substrates (OCTN2)?
- Quinidine
- Verapamil
- Imatinib
- Valproic acid
- alphamethyldopaphenylalanine
- Valacyclovir
34
Examples of Organic Anion Transporting polypeptide (OATP2B1) substrates:
- Pravastatin
- Rosuvastatin
- Atorvastatin
- Fexofenadine
(remember statins)
35
How can transporters be detrimental to drug absorption?
- Efflux transporters (eject compound from cell) thereby reducing drug absorption.
36
What are P-glycoproteins?
Efflux pumps.
37
What are some examples of Pgp substrates?
- HIV PI
- Immunosupressants
- Antibiotics
- Cardiotonics (digoxin)
- VERY DIFFICULT TO GIVE CANCER DRUGS ORALLY
38
All oral anticancer drugs are substrates for Pgp efflux pump.
True or False?
True
39
Is Doxorubicin a Pgp substrate?
Yes -
40
Name 2 Digoxin drug drug interactions
Digoxin and ritonavir
Digoxin and atorvastatin
Both increase digoxin AUC
41
What is Dyspepsia?
Persistant or recurrent pain or discomfort in upper abdomen.
42
Causes of Dyspepsia?
- Lifestyle factors
- Medication
- Disease
43
What is GORD and what are the symptoms?
Gastro Oesophageal Reflux Disease.
Complications resulting from reflux gastric contents into oesophagus, oral cavity or lung such as stricture, barrets oesophagus and oesophageal carcinoma.
44
Causes of GORD:
- Obesity
- Genetic
- Lifestyle
- Medication
- Age
45
What are peptic ulcers?
- Open sores on the inside lining of oesophagus, stomach and upper portion of small intestine.
46
Causes of peptic ulcer?
- H pylori
- NSAIDS
- Lifestyle factors
- Genetics
47
Definition of peptic ulcer:
Breach in continuity of epithelial lining of more than 5mm in diameter associated with inflammation.
48
What is the difference between a gastric ulcer and a duodenal ulcer?
GASTRIC ULCER -->
- Pain radiates to back
- Mainly occurs at night
- Aggravated by food
- Loss of weight
DUODENAL ULCER-->
- Eipgastric pain
- Anytime - empty stomach
- Relieved by food/antacids
- Weight gain
49
Management of ulcers?
- Medicine management
- Smoking cessation
- Avoid acidic food and drink
- avoid eating late in evening
- Weight reduction
- Reduce stress
50
What is ALARMS?
```
Warning signs for ulcers:
A = anaemia
L = loss of weight
A = Anorexia
R = Recurrent
M = melaena
S = swallowing problems
```
51
What are the required assessments for ulcers?
- Medicine review
- Blood test
- H pylori testing
- X ray
- Endoscopy
52
What are antacids used for and what are some of their side effects?
Ulcer
- they neutralise stomach acid
- Simple cheap and effective
- Dosage = PRN
- Side effects -->
magnesium = laxative effect
aluminium = constipation
calcium containing = possible rebound acid secretion.
53
Can sodium bicarbonate be prescribed on its own?
No - but present in some other preparations.
| To be avoided if patient is on a salt restricted diet.
54
Interactions of antacids:
- May impair action of drugs taken at same time
- can damage enteric coating by raising the pH
- Rarely may affect pH dependent renal excretion
55
What is an alginate?
- Drug given in combo with an antacid
| - Increase viscosity of stomach contents
56
How does an alginate work?
Forms raft that floats on top of stomach contents.
57
What is the daily dose of H2 receptor antagonists ?
BD
58
Are H2 receptor antagonists available OTC?
Yes - they are generally safe and well tolerated. example Ranitidine (Zantac)
59
Name some interactions of H2 receptor antagonist Cimetidine:
- Warfarin
- Theophylline
- Sildenafil
- Phenytoin, carbamazepine, valproate,
60
Are PPI's available OTC?
Yes
61
Indications of PPI's
- Dyspepsia
- GORD
- Treatment of gastric and duodenal ulcers
- NSAID prophylaxis
62
Side effects of PPI's
Headache, constipation, diarrhoea, dizziness
| MHRA warning - SCLE (sub cutaneous lupus erythematosus)
63
What are some of the consequences of long term PPI use?
- gastric cancer
- H pylori infection
- Pneumonia
- Clostridium difficile infection
- Bacterial overgrowth and reduced calcium absorption leading to hip fracture.
64
Name some interactions of PPI's:
- antiretro virals
- methotrexate
- citalopram
- predicted to decrease efficiency of clopidogrel
65
Helicobacter pylori always castes gastritis, true or false?
True
66
How is H. Pylori detected?
- Antibody response detectable in serum, salvia or urine.
| - Antigen detectable in stool
67
Testing that is required for H Pylori:
- Urea breath test kits
- Stool antigen test
- Mucosal biopsies
- Lab based serology
68
Antibiotics can surpress H Pylori growth and give a false negative. True or false?
True
69
Rules of testing for H Pylori:
Testing should not be performed within 4 weeks of treatment with antibacterials or 2 weeks with PPI drugs.
70
Consequences of NSAIDS:
Variety of GI injuries including PUD bleeding and ulceration.
71
What is the mechanism of NSAID induced ulcers:
- Inhibition of prostaglandins synthesis impairs mucosal defences (erosive breach of epithelial layer)
- Acid attack deepens breach into frank ulceration
72
What is the indirect mechanism of NSAID induced ulceration:
Reduced gastric blood flow and reduced mucus production leads to decreased cell repair.
73
Management against NSAID induced GI injury:
- Stop NSAID if possible
- Test for H Pylori
- Treat with full dose of PPI or H2 receptor antagonist for 8 weeks.
74
Name a medication that prevents NSAID induced PUD.:
Misoprostol
75
Misoprostol mechanism of action?
Prostaglandin analogue - less well tolerated than PPI's
| - Also a drug used to terminate pregnancy
76
What are the two examples of Inflammatory Bowel Disease?
1. Crohn's disease
| 2. Ulcerative colitis
77
What is the peak age of diagnosis in Inflammatory Bowel Disease?
10 - 25
78
Most common side effect o Inflammatory Bowel Disease?
Diarrhoea
79
What is IBD?
Inflammation of the gastric mucosa
80
Difference between Crohns disease and ulcertaive colitis:
CD = whole of GI tract from mouth to anus and affects all layers
UC = affects mucosa of colon and rectum
only mucosal and submucosal layers involved.
81
Causes of Inflammatory Bowel Disease?
Precise mechanism unknown - likely to be a combo of factors such as:
- Genetic
- Environmental
- Gut microbes
- Smoking
- Infection
- Diet
- Medication
82
IBD signs and symptoms?
```
Abdo pain
Diarrhoea
Fatigue
Anaemia
Weight loss
Fever
```
(Can get extraintestinal manifestation) e.g. swollen joints, eye problems
83
Consequence of Crohns:
Strictures: narrowed segments of bowel --> leads to blockages
Fistulas: abnormal channels lined with granulation tissue --> form between intestine and skin
84
Investigations required for Crohns:
- Blood test (full blood count, thyroid function, liver function, urea and electrolytes, inflammatory markers)
- Stool culture
- Faecal calprotectin (distinguishes between CD and UC)
- Endoscopy
- Colonoscopy
- Biopsies
- Abdo imaging.
85
What is the CDAI?
Crohns Disease Activity Index
86
Aims of management of IBD?
- Achieving remission
- Mainting remission
- Improving QoL
87
What are the 5 treatments for IBD?
- Corticosteroids
- Aminosalicylates
- Immunomodulating agents
- Antibiotics
- Novel treatments
88
How are Corticosteroids used in IBD treatment?
- Induce remission
- Reduce inflammation
- Oral or IV used
- Mustn't be stopped abruptly --> adrenal supression
```
Oral = prednisolone 40mg daily
IV = acute severe, hydrocortisone 100mg ads
```
89
Do corticosteroids prevent progression of IBD?
No - they just induce remission.
90
Side effects of corticosteroids:
- GI side effects
- Fluid and electrolyte balance
- Increased appetite
- Hypertension
- Infection risk
- Risk of development of osteoporosis
91
How are aminosalicylates used in IBD treatment?
- anti inflammatory action
- Induce and maintain remission
- Mostly used for UC
- Can give topical and oral together if required.
92
Give two examples of aminosalicylates
Sulfasalazine
| Mesalazine
93
Monitoring requirements for aminosalicylates:
- Renal Function
| - Blood dyscresias
94
How are thiopurines used in IBD treatment?
- Induce and maintain remission
- First line Immunomodulators for IBD
- Can take 3-6 months for full effects
95
Example of thiopurine:
Azathioprine (prodrug)
| Weight based dosing
96
What are TMPT levels?
Thiopurine methyl transferase.
| Must be recorded when taking thiopurines.
97
What other immunomodulators are used in IBD apart from thiopurine?
- Methotrexate (mainly for maintenance in CD) once weekly
(sometimes coprescribed with folic acid)
- Tacrolimus- induces remission in mild moderate UC
- Ciclosporin induces remission in severe UC
98
What biologics are used in IBD and what is there mode of action?
E.g. Infliximab
- Monoclonal antibodies
- Work by binding to tumour necrosis factor a
- Inhibit inflammatory effects in gut
99
How is infliximab administrated?
IV
100
Future therapies of IBD?
- Faecal microbiota transplant
- Probiotics
- New biologics
101
What is the WHO definition of diarrhoea?
Passage of 3 or more loose liquid stools per day
102
How is diarrhoea categorised?
Acute < 14 days
Persistant > 14 days
Chronic > 28 days
103
Causes of diarrhoea?
- Increased osmotic load in gut lumen
- Increased intestinal motility
- Increased secretion
Other causes= drugs, parasites, anxiety
ecoli, salmonella
104
When would you refer an adult with diarrhoea?
```
Symptoms:
>72 hours in healthy adults
>48 hours in elderly
>24 hours in diabetics
- Associated severe vomiting
- blood/mucus in stools
- ADR
- Weightloss
- Rectal pain
```
105
What treatment is available for diarrhoea?
- Oral rehydration therapy
- Loperamide
- Morphine
- Diphenoxylate
- Adsorbents
- Antibiotics
106
How does oral rehydration therapy work?
- enhances absorption of water and electrolytes
- contain alkalinising agent to counter acidosis
- Must be slightly hypo-osmolar
107
What ingredients do oral rehydration therapies usually contain?
- Na and K to replace essential ions
| - Citrate and/or bicarbonate to prevent acidosis
108
How does loperamide work?
- it is a synthetic opioid analogue
- Reduces peristalsis so faeces stays in gut for longer
- Cant be used In active ulcerative colitis
- MHRA ALERT - serious cardiac ADR
109
When are antibiotics used in diarrhoea treatment?
Only if confirmed infection in stool sample
110
How does morphine work in diarrhoea treatment ?
Direct action on intestinal smooth muscle
111
How does diphenoxylate work in diarrhoea treatment?
Synthetic derivative of pethidine
112
How does absorbents work in diarrhoea treatment?
absorb microbial toxins and microorganisms e.g. kaolin
113
What is the rotavirus vaccine?
A live oral vaccine that protects young children against gastroenteritis infection.
2 doses:
- First at 2 months of age
- 2nd at 3 months (at least 4 weeks after last one)
- Course should be completed before 25 weeks of age
114
What is clostridium difficile?
- Spore producing, anaerobic, gram positive anaerobic bacterium.
- Caused by antibiotics
115
Clostridium difficile antimicrobial treatment?
- Oral metronidazole 400mg ads
- Oral vancomycin - sever disease oral 125mg every 4 hours
- probiotics, faecal microbiota transplant and iv immunoglobulin used also
116
How many types of stool classified in Bristol stool chart?
1-7
117
What are the two cases of constipation?
Functional - no anatomical cause known
Secondary - induced by particular condition or medicine
118
Constipation treatment?
Lifestyle intervention:
- Diet (fibre)
- Fluids
- Lifestyle measures
LAXATIVES
119
What are the four type of laxatives available? Explain.
1. Bulk forming - increase faecal mass to stimulate peristalsis e.g. methyl cellulose
2. Stimulant - increase intestinal motility via muscle contractions e.g. Senna
3. Osmotic - draw water into intestine by osmosis e.g. macrogel powders.
4. Faecal softening - stimulate peristalsis by increasing Faecal mass
e. g. glycerol suppositiory
120
What is coeliac disease?
- Autoimmune disease
- Affects small bowel
- NOT ALLERGIC REACTION
121
How is coeliac diagnosed?
Serology or endoscopy
