GI System Flashcards
1
Q
What is the sub muscosa?
A
Connective tissue, allowing tract to distend & be elastic.
Contains larger blood & lymph vessels -> sends branches to muscosa & muscularis mucosa
2
Q
What is the muscularis externa?
A
Major smooth muscle comprised of 2 layers:
- Inner circular mayers
- Outer longtitudinal laters.
Responsible to mixing & propulsive movements.
Myenteric nevere plexus lives between 2 the 2 layers
3
Q
What is the function of the autonomic smooth muscle?
A
Self induced electrical activity in digestice smooth muscle. Electrical activity is induced by cells of Cajal.
Reaching the threshold to induce contraction depends on mechanical, neural& hormonal factors.
4
Q
What are the receptors found in the GI tract?
A
Chemoreceptors, mechanoreceptors, osmoreceptors.
Stimulation results in neuronal reflexes or secretion of hormones which alter avidity of effector cells.
5
Q
What hormones are released in the stomach?
A
Ghrelin
Gastrin
6
Q
Wht hormones are released in the duodenum?
A
Cholecytokinin
Sectretin
GIP
Motilin
7
Q
What hormones are released in the pancreas?
A
Insulin
Glucagon
Pancreatic polypeptide
Amylin
8
Q
What hormones are released in the small intestine?
A
GLP-1
GLP-2
Oxyntomodulin
PYY3-36
9
Q
What does trypsinogen do?
A
Converted to active form trypsin by enterokinase.
10
Q
What does chymotrypsinogen do?
A
Converted to active form chymotrysin
11
Q
What does procarboxypeptidase do?
A
Converted to active form of carboxypeptidase.
12
Q
What does pancreatic amylase do?
A
Only enzyme secreted throughout entire digestive system that can digest fat.
13
Q
What does pancreatic lipase do?
A
Only enzyme secreted throughout entire digestive system that can digest fat.
14
Q
What does bile contain?
A
Bile salts, Cholesterol, lecithin, bilirubin
15
Q
What is bile salts
A
Derivatives of cholesterol, convert fat globules into liquid emulsion.
16
Q
How are carbohydrates absorbed?
A
1 - Polysaccharide starch & glycogen converted into disaccharide through action of salivary & pancreatic amylase.
2 - Maltase dissacha
17
Q
Where & how is stomach acid produced?
A
Produced in the parietal cells in the canaliuli. Stimulated by Histamine, gastrin ACh.
Gastrin production stimulated by vagal stimuli, this increases the pH & ingested protein & Ca2+.
18
Q
What does somatostatin do in the stomach?
A
Increases mucus secretion, Increases bicarbonate, Increases blood flow & decrease acid production.
19
Q
What is Helicobacter Pylori (H.pylori)?
A
Bacteria that colonises itself beneath the mucus layer in the antrum -> chronic inflammation. decreased somatostatin, increased gastrin production -> increased acid.
Increased acid means chronic inflammation in duodenum. H.pylori moves into duodenum and causes a duodenal ulcer.
20
Q
How is H.pylori identified?
A
Given radio labelled urea & CO2 produced in breath.
Stool sample needs to be stored at -20C before testing.
21
Q
What are the risk factors of PUD?
A
H.pylori is a major cause of PUD
NSAID common cause of PUD
More common in smokers.
22
Q
What drugs can induce dyspepsia?
A
NSAIDS
Sulfasalazine
Iron preparations
CC
Bisphosphinates.
Theophylline
23
Q
What are the symptoms of gastric ulcer?
A
Pain on eating, epigastric pain
24
Q
What are the symptoms of Duodenal ulcer?
A
Localised pain occurring between meals and at night.
25
What is GORD?
Condition caused by gastric juice & occasionally duodenal contents in oesophagus.
Defective Lower Oesophageal sphincter may be most important abnormality.
26
What factors can cause the lowering pressure of the LOS?
Dietary factors
Smoking
Endocrine factors
Drugs
27
What is a hiatus hernia?
Where part of the stomach is pushed up through the diaphragm, prevents LOS from closing, allowing stomach contents to escape.
28
Drugs that can cause GORD?
Anticholinergics
B-2 Agonists
CCB
Diazepam
Nitrates
Alcohol
Progesterone
Oral Contraceptives
Theophylline
29
Drugs that cause ulcers?
NSAIDs
Bisphosphonates
Clindamycin
Cotrimoxazole
Doxycycline
K
Theophylline
Tetracyclic AD
30
What are the 4 groups of functional dyspepsia?
Ulcer like
Dysmotility like
Reflux like
Non-specific
31
How do you manage stomach & duodenal ulcers?
Identify & eradicate H.pylori
Stop inappropriate therapy
Decrease acid prod to reduce gastritis & enable mucosa to repair (H2 antagonist/ PPI)
32
How do you manage GORD?
Remove causative agents
Use of rafting products
Reduce acid prod to enable recovery of oesophageal mucosa.
33
What are the non-pharmacological advice for GORD?
Diet:
- Eat small meals
- Avoid food which decrease pressure of LOS
Avoid eating within 4 & drinking within 2 hours of going to bed
Avoid tight fitting cloths
Lose weight
34
What are Antacids?
Aluminium, magnesium, Sodium & Calcium salts.
These neutralise stomach acid but cause belching.
Rapid relief of symptoms of heartburn & indigestion.
Avoid long term use.
35
What are the S/E of antacids?
Constipation with aluminium
- Al binds phosphates in the gut -> osteoporosis
- Al may be absorbed -> nephrotoxic
36
What are Alginates?
These come with antacids and form a high pH viscus mass (Raft) trapping air bubbles & CO2 from the reaction of antacid with stomach contents.
This raft floats to the top of the stomach and protects oesophageal mucosa from stomach contents.
37
What is Dimethicone?
Anti-foaming agent
Reduce the surface tension of intragastric air bubbles
Allow bubbles to escape -> reduce bloating feeling.
38
What are H2 antagonists?
Class of drugs that compete for H2 receptors on the parietal cells.
Can be overridden by a powerful stimulus such as a large meal.
39
What are the S/E of H2 antagonists?
Headache & dizziness.
Cimetidine - Gyno 0.2%
Nizatidine - Sweating, abnormal dreams
Cimetidine binds to CYP450
40
What are PPI?
Drugs that are enteric coated to absorbed in the small intestine.
Prolonged suppression of acid secretion.
Heal uclers rapidly than H2 antagonists.
Superior treatment of reflux / GORD.
41
What are the S/E of PPI?
Nausea, diarrhoea, flatulence, epigastric pain, dry mouth & headache.
42
When should you refer someone to the GP when taking PPI?
After 2 weeks treatment there's no improvement.
Treatment required continuously for 4 weeks then refer
Pt is over 45 & present with new or changed symptoms.
Weight loss, loss of appetite, signs of anaemia, dysphagia .
43
What treatments should be used for dyspepsia, gastritis, PUD?
Removal of causative agents.
Dietary changes
Symptomatic treatment.
H2 antagonists/PPI
44
What treatments should be used for GORD?
Lifestyle & dietary changes
Alginate products / PPI
NOT H2 ANTAGONISTS .
45
What is constipation?
Passage of hard stool less frequently than Pt own pattern.
Difficulty in opening bowl:
- Going <3X per week
- Straining to open bowls more than 25% of occasions.
- Hard or pellet like stool more than 25% of occasions.
46
What is chronic constipation classes as?
>12 weeks in preceding 6 months.
47
What medications cause constipation?
Antacids.
Antispasmodics.
Antidepressants.
Iron tablets.
Diuretics.
Painkillers.
CCB.
Anti cholinergic
Ulcer healing.
Laxative abuse.
48
What intestinal obstruction cause constipation?
Scarring from IBD, Diverticulitis
Adhesions
intestinal cancer
Abdominal hernia
Gallstones wedged in intestine
Volvulus
Foreign bodies
Haemorrhoids
Fissures.
49
How would you diagnose constipation?
Medical history
History of symptoms:
- Normal patterns of shifting
- Other symptoms
- Frequency & consistency
- How long / Intense are the symptoms
- Impact on daily life.
Medication
Changes in diet & lifestyle
50
What are the goals in constipation management?
Achieve individual normal frequency of shitting
Establish regular comfortable shit
Preventing laxative dependence
Relieving discomfort.
51
Name some bulking agents
Ispaghula husk
Methylcellulose
52
Name some stimulant laxatives
Bisacodyl
Senna
Dentron
Sodium picosulphate
53
Name some faecal softeners
Docusate
Glycerol
Arachis oil
54
Name some osmotic laxatives
Lactulose
Macrogols
Mg
55
What is the acute treatment of constipation in Adults?
1 - Lifestyle + manage underlying cause
2 - Bulk forming (+/or) osmotic - macrogol
3 - Stimulant (Gradually reduce + stop after producing a soft, formed stool without straining at least >3X per week).
56
What is the chronic treatment of constipation in adults?
1 - Lifestyle + manage underlying cause
2 - Bulk forming (+/or) osmotic - macrogol
3 - Stimulant
4 - Prucaptopride
Gradually titrate the laxative doses up/down aiming to produce soft, formed stool without straining >3X per week.
57
What is the treatment constipation in pregnant people?
1 - Offer bulk forming
2 - ADD/Switch to osmotic
3 - Can consider a short course of stimulant
4 - Glycerol suppository.
58
What is the treatment of constipation in someone who is breast feeding?
1 - Offer bulk forming
2 - ADD/Switch to osmotic
3 - Can consider a short course of stimulant (Senna/Bisacodyl)
4 - Glycerol suppository.
59
What would you give for hard stool faecal impaction / Loading ?
1 - High dose of oral macrogol
2 - Stimulant reduce inadequate / slow
3 - Glycerol alone or with Bisacodyl suppositories
- Response still inadequate - Sodium phosphate / arachis oil retention enema.
60
What is the treatment for opioid induced constipation?
Avoid bulk forming laxatives.
1 - Osmotic (or docusate) + stimulant
2 - Naloxegol :
- Peripherally acting mu-opioid receptor antagonist.
- Oral
3 - Mehtylnaltrexone :
- Pamora
- S/C
4 - Naldemdine :
- Pamora
- Oral
61
What is the treatment of constipation in children?
1 - Macrogels & negotiated + non punitive b/h interventions suited to persons of development.
2 - Add stimulant
3 - Add lactulose
62
What is the lifestyle advice you would give someone with constipation?
high fibre diet & sufficient fluid
63
What is the pharmacology of bulk forming laxatives?
Mimic polysaccharides so increase osmolarity in the gut when broken which causes water retention. Water retention causes softening of stool. Promotion of peristalsis via stimulating colonic mucosal receptors this leads to ACh release. ACh activates muscarinic ACh receptors which increases peristalsis
64
What is the pharmacology of Osmotic laxatives?
These are poorly absorbed so they act as osmotic agents which increase water retention. These are hyperosmolar agents, absorbed into stool by osmosis. Mg2 triggers release of cholecytokinin (CCK) this increases intestinal secretions & colonic motility. Which decreases transit time through the gut.
65
What is the pharmacology of stimulant laxatives?
Stimulate local reflexes of the myenteric nerve plexus of the gut. Irritate nerve endings in wall of intestine. Motor effect on gut wall increases propulsion. Increase secretion of H20 into bowl, increases gut motility & decrease transit time.
66
What is the pharmacology of Senna?
It is anthraquinone laxative. Combine with sugars -> glycosides. Glycosides molecules where sugars is attached to functional group via glycosidic bond. Glycosidic bonf hydrolysed by colonic bacteria to release irritant antracene glycoside, sennosides A&B. These are absorbed and have a direct action on the myenteric nerve plexus. Also postulated to increase PGE2 secretion and decrease colonic H20 absorption.
67
What is the pharmacology of stool softeners?
Emollient laxatives. Work as a surface wetting agent / surfactant. Decrease surface tension allows H20/Fat to penetrate stool.
68
What do PAMORA do?
Prevent opioid activator of intestinal mu-opioid receptor.
69
What is the pharmacology if prucalopride?
5HT4 receptor agonist
Which causes an increase release of ACh which then increase parasympathetic drive which increase peristalsis
70
What are the RED FLAG symptoms?
Pain on defication
Pt over 40
greater than 14 days
Associated fatigue
Presence of blood
Repeated failure of laxatives.
71
What is chronic diarrhoea?
When its lasts more than 14 days
72
What is the pathophysiology?
Change in balance between the absorption & secretion of water & electrolytes. Osmotic force drives water into the gut lumen.
73
What is the mechanism of diarrhoea which is caused by bacteria??
Invasive:
Directly attack mucosal cells which cause diarrhoea.
Stools may contain puss & blood.
Non-Invasive:
Do not DMG gut
Bacteria produce enterotoxins that disrupt secretions
74
What drugs cause diarrhoea?
Antibiotics
Laxatives
Metformin
Ferrous sulphate
NSAIDs
Cholestyramine
Antacids
Digoxin
75
What is the treatment of acute diarrhoea in adults?
Prevention & reversal of fluid & electrolyte depletion
Management of dehydration ]
ORT
Eat bland food
Stool bulking fruits
Avoid alcohol, caffeine
76
What is the pharmacology of Loperamide?
Binds to mu-opioid receptors in gut wall.
Doesnt cross BBB
--| ACh
ACh bind to muscarinic/nicotinic ACh receptors which increase parasympathetic activity.
77
What are the red flags to refer?
Recent travel abroad
Blood/mucus in stool
Associated with severe vomiting and fever
Signs of dehydration.
78
What medications should you stop taking while having diarrhoea for 24-48 hours?
ACE-i, ARB, Diuretics, Metformin.
79
What is C.diff?
Board spectrum antibiotics upset the microbiome allowing C.diff to flourish.
80
What is the treatment for C.diff?
Vancomycin 125-500mg every 6 hrs for 10 days
81
What is the symptoms of IBS?
Abdominal cramping
Diarrhoea, constipation, alternating
Farting
Bloating
Urge to shit
Acid indigestion
Nausea
Lethargy
Eating may worsen symptoms
Passing mucus in the stool
82
What are the red flags & referral of IBS?
Unintentional weight loss
Unexplained rectal bleeding
Loose stool for >6weeks in Pt over 60 yrs
Anaemia
83
Describe the pathophysiology of CD?
Can affect any part of the GUT
Usually terminal ileium & ascending colon.
Affected areas are thickened, deep ulcer can appear, can progress to deep fissuring uclers
84
What are the clinical features of both UC/CD?
* Diarrhoea
* Fever
* Abdominal pain
* N&V (More common in CD)
* Malaise
* Weight Loss (More common in CD)
* Malabsorption
85
What clinical features are unique to CD?
* More debilitating that UC
* Can be acute / insidious
* Palpabke masses
* Small bowel obstruction
* Abcesses
* Fistulas
86
What are the complication of IBD
* Osteopenia
* Erythema Nodosum - Tender, hot red nodules, subside in a few days.
* Pyoderma Gangrenosum
* Ocular Episclritis - Intense burning & itching of blood vessels involved.
87
What is P-ANCA present in?
-VE in CD
+VE in UC
88
What is the MOA of CC?
Positively transporting themselves into target cells & binding the intracellular CC receptor du to being membrane bound to heat shock protein complex. When CC binds to GRalpha its activated of homodimer of 2 activated GR transported into nucleus of target cell. This --| promoter regions of genes such as NFKB & AP-1
89
What is the MOA of azathioprine?
Azathioprine is converted to 6-MP. This is then activated by HGPRT &TPMT. 6-TGN is then slotted into DNA.
Another pathway forms Xanthine oxidase to form 6-Thiouric Acid. 6-Thio - GTP binds to Rac-1 instead of GTP. Activation of Rac-1 target genes such as MEK, NKFB, BCL-XL.
90
What is the MOA of 5-aminosalcylates?
* Have an action on both PG synthesis/cyclooxygenase pathway and supression of pro-inflammatory cytokines
* Actions of PG synthesis comes VIA COX --|
* Actions on supression of cytokines comes via --| of PPARgamma, NF.kB & other non-COX targets.
* Can also scavange reactive oxygen metabolites. from superoxide anion generation by neutrophils which can in turn prevent DNA & tissue DMG.
91
How does TNFα work?
TNFα activates macrophages to produce proinflammatory cytokines -> increase apoptosis of gut epithelial cells -> regulates T cells apoptosis -> paneth cell death vai necropoptosis.
92
What mediators cause Crohns Disease?
TH1 - IFNγ, TNF, IL-6
TH17- IL-17A/F, IL-21, IL-22
93
What mediators cause Ulerative collitis?
TH2 - IL-5, IL-6, IL-13, TNF
TH9 - IL-9
TH17 - IL17A/F, IL-21, IL-22
94
What mediators cause resolution in healthy cells?
IL-10, TGF-β
95
How does inflixumab work?
Human monoclonal antibodies that bind both soluble & trans membrane bioreactive forms of human TNFα -> prevents binding of TNFα to receptors -> --| biological activity of TNFα
96
What is the MOA of Ustekinumab?
Monoclonal antibody targetting P40 subunit of IL-12 & IL-23. --| of IL-12 & IL-23 supress TH1 & TH17 cells linage of cytokines & chemokines in IBD
97
Describe T-Cell homing IBD?
* In IBD, T-cells migrate/home towards gut tissue when they accumulate in large numbers and secrete inflammatory mediators (IL-6, IL-23, TNFα)
* T-cell homing to the gut requires an interaction between 2 molecules; one on the surfae of the T-cell and on the endothelial cell.
* T-cell surface integrin, α4β7, is a gut specific adhesion molecule that specifically ineractis with mucosal vascular adression adhesion molecule (MAdCAM1) that is expressed in the endothelium.
* T-cells are also reatined in the gut tissue through binding of the α4β7 integrin to the E-cadherin on the basal membrane of the epithelial cell.
98
What is the MOA of Vedolizumab?
Anti α4β7 antibody blocking homing of T-cells to the inflammed gut.
99
What is the signalling pathway for Sphingosine 1 - Phosphate?
S1P receptor controls egression of the immune cells from lymph nodes through a [ ] gradient on sphinosine 1 phosphate. S1PR1 agonists render lymphocytes sensing the S1P gradient and exiting lymph therefore causing a reduction in lymphocytes.
100
What is the aim of UC therapy?
* Reduce inflammation
* Induce remission
* maintain remission
* Improve QOL
* Minimise toxicity related to drugs
* Maintain therapy used to maintain remission
101
What is the treatment for proctitis UC?
* Topical aminosalicylates
* Add oral aminosalicylate if remmision not achieved in 4 weeks
* For Pt that cannot tolerate aminosalicylates consider time limited oral/topical CC
102
What is the treatment for proctosigmoiditits & distal colitis UC?
* Topical aminosalicylates
* If remissoin not achieved in 4 weeks consider high dose oral aminosalicylates or switching to high dose oral aminosalicylates + time limited topical CC
* if this still doesnt work then oral aminosalicylates + oral CC
103
What is the treatment for extenisve UC?
* Topical aminosalicylates + high dose oral aminosalicylates
* no remission in 4 weeks then stop troical treatment & offer time limited course of oral CC
* For ppl who cannot tolerate aminosalicylates -> time limited oral CC
104
What is the treatment to induce remission is moderate to severe UC?
* Biologics & JAK
* Infliximan & adalinumab
105
What is the treatment to induce ression in acute hospitalised?
* IV CC & assess likelihood of requireing surgery
* Consider IV ciclosporin / surgery intolerant / decline / CI CC
106
What is the treatment of proctitis & proctosigmoiditis - maintaining remmison in UC?
* Topical aminosalicylate alone
* Oral aminosalicylate + Topical aminosalicylate
* Oral aminosalicylate if Pt decline topical treatment.
107
What is the treatment to maintain remission in mild - moderate UC?
* Offer low maintenance dose of oral aminosalicylate.
108
What treatment should be used to maintain remission in all areas?
* Consider mercaptopurine / azathioprine.
109
What is the treatment for inducing remission in CD?
Monotherapy with traditional CC (Prednisolone, hydrocortisone IV)
110
What is the treatment for inducing remission for add on therapy?
* Consider + azathioprine / mercaptopurine to CC / budesonide to induce remission.
* Consider adding MTX to CC / Budesonide in those who cant tolerate azathioprine / mercaptopurine or lower TPMT activity.
111
What used in maintaining remission in CD?
* Azathioprine / mercaptopurine
* Consider MTX in those who need it.
112
What are the S/E of aminosalicylates?
* Headache, nausea, fever, rash, raised temp, decreased WBC
* Pancreatitis
* Hepatitis, pneumonia, skin reactions, haemolysis, inflammation of the kidney
113
What should be checked before starting Thiopurines?
* FBC, U&E, LFT
* Screen of HCV, HIV, HBV / VZV
* Vaccinated influenza & pneumococcal
114
What should be monitored while on thiopurines?
* FBC, U&E, LFT at least 2, 4 8 & 12 then 3 monthly
115
What should the PT report if they're on thiopurines?
* Ulceration
* Fever
* Infection
* Bruising
* Bleeding
116
What should you reduce the dose of azathioprine by when you are taking both allopurinol and azathioprine?
1/4
117
