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home - Stomach - Peptic Ulcer Disease - NSAID Pathophysiology Written by Dr Sebastian Zeki

Knows the range of organic and non-organic causes of dyspepsia. Be
aware of current BSG and NICE guidelines for selecting patients for
investigation. Know the significance of alarm symptoms
Understands the relevance of Helicobacter pylori infection and how it
can be detected and treated.
Recognise the adverse effect of nonsteroidal anti-inflammatory drugs
Understands the physiology of gastric acid secretion, mucosal
protection and gastroduodenal motility and know how drugs can
modify these
Knows the complications of ulcer disease, the principles of surgery
that may be required and be aware of post-operative sequelae

Makes a thorough clinical assessment, perform appropriate
investigations and be familiar with how medical treatments are used.
Show awareness of how to recognise and manage complications

Can explain the steps taken towards making a diagnosis and
planning treatment clearly and comprehensibly


Knows the causes of upper gastrointestinal bleeding and its
Understands the circulatory disturbance associated with blood loss
and the pathophysiology underlying the clinical manifestations of
hypovolaemic shock
Knows the principles of assessing hypovolaemia and of restoring the
circulation. Be able to identify and correct coagulopathy
Knows the principles of using the various risk stratification tools SCE 1
Knows how endoscopic techniques are used to control bleeding CbD, DOPS, SCE 1
Understands how oesophageal and gastric varices develop and the
endoscopic and pharmacological methods that are used to control
blood loss

Can make an accurate clinical assessment, and stratify the risk. Know
the principles of fluid resuscitation and arrange endoscopy
Is aware of methods to secure haemostasis, recognise signs of rebleeding and liaise with other disciplines (such as interventional
radiology or surgery

Assesses and treats patients who have bleeding with appropriate
degree of urgency.


Understands why part or all of the patient’s stomach is removed and
the altered post-surgical anatomy

Understands the problems of a gastro-enterostomy and a Roux-en-y

Has awareness of dumping syndromes
Knows the various surgical operations performed for obesity (bariatric
surgery) and their complications

Can give nutritional advice and choose the appropriate method by
which an enteral feeding tube is inserted into the small bowel

Can initiate the use of pancreatic enzyme therapy
Has ability to recognise and treat early and late dumping syndrome
Able to help the patient carers friends and family understand how
the patient can be encouraged to gain weight

Works closely with dieticians and surgical colleagues

NSAID Pathophysiology

Risk of Gastrointestinal ComplicationsGI probs are most common within the first 3/12 after the initiation of therapy.Even low dose aspirin can be associated with a significant decreased gastric mucosal [PG].Polymorphism of cytochrome P450 2C9 may delay NSAID metabolism.There is no correlation between symptoms and pathology.The risk of toxicity may not be uniform among the NSAIDs.The risk of GI complications was highest with indomethacin (relative risk {RR} 2.25) followed by naproxen (RR 1.83), diclofenac (RR 1.73), piroxicam (RR 1.66), tenoxicam (RR 1.43), ibuprofen (RR 1.43), and meloxicam (RR 1.24).The GI risk is related to the NSAID treatment dose and duration. NSAIDS and GI toxicity NSAIDs unionized- acidic ph has no effect ionized in mucosa Minimal Damage but not main cause of ulcers Arachidonic acid PGG2 PGH2 PGE2- Gastric and duodenal mucosa COX-1 NSAIDs COX-3- The brain, heart, and aorta -with levels in brain tissue around 5 % of those of COX-1COX-3 in the brain may be one target of paracetamol.COX-2 selective inhibitors (eg celecoxib and etodolac) may still block COX-1 at clinically recommended doses and thus have the potential to also block COX-1 in the stomach and duodenum and cause damage.Although aspirin inhibits COX-1 and also COX-2, certain COX-2-mediated reactions can still occur after aspirin has been given, allowing for some ongoing mucosal protection.Therefore, the combination of low-dose aspirin and a COX-2 selective inhibitor may lead to more GI damage than low-dose aspirin alone. Stimulates:-Glycoprotein (mucin) secretion -Bicarbonate secretion-Phospholipid secretion-Enhancement of mucosal blood flow and oxygen delivery to cells via local vasodilation -Increased epithelial cell migration towards the luminal surface (restitution) -Enhanced epithelial cell proliferation Mucosal protection Nitric oxide Neuronal NOS (nNOS, type I) Endothelial NOS (eNOS, type III) -Mediation of the release of gastric mucus -Stimulation of fluid secretion -Maintenance of epithelial barrier function -Enhancement of mucosal blood flow Big damage Increased mucosal permeability to hydrogen ions and to sodium ions Repair mechanisms -Rapid migration of deeper epithelial cells lining gastric pits to cover the damaged surface (restitution) -Less rapid regeneration of new epithelial cells from progenitor cells (proliferation). Oedema, erythema, subepithelial hemorrhage, erosions (mucosal breaks, without visible depth to the lesion), and ulcers (mucosal breaks, with visible depth to lesion). NSAIDs Associated GU Toxicity Risk Factors:Increasing patient age, particularly >60 .Higher NSAID dose(s).A past history of gastroduodenal toxicity from NSAIDs.A past history of peptic ulcer disease.Concurrent use of glucocorticoids, anticoagulants, bisphosphonates, or other NSAIDs. NSAID - Gastric erosions of 50% NSAID users - Quarter with dyspepsia had ulcers - 50% with PUD due to ulcers are asymptomatic - Complication higher if previous PUD NSAID GI complications include a)Gastric ulcer b)Colitis c)Not oesophagitis Risk factors for an acute NSAID gastritis More than 65 Previous bleed Anticoagulation High dose NSAID H. pylori Steroids Debilitation Mechanisms of Mucosal Protection In the GI Tract Retard diffusion from lumen into mucosa COX -2 15-hydroxyei-cosatetrae-noic acid (15-HETE) Arachi-donic acid 15-epi lipoxin A4 5-lipoxygenase (5-LOX). (a constitutive enzyme) Expressed in many cells only when bacterial polysaccharides, pro-inflammatory cytokines such as TNFa or IL-1b, or growth factors (mitogens) induce its expression. NSAID induced gastric toxicity other than via COXNSAIDs probably interfere with growth factors and other mediators responsible for restitution and adaptive protection further contribut-ing to their toxicity. Role of Helicobacter pylori infectionThe role in NSAID-induced gastritis or ulcer formation is complex.The risk of uncomplicated peptic ulcer disease was significantly higher among H. pylori positive compared with H. pylori negative NSAID users (OR 1.81). Epithelial restitution and prolifera-tion both require adequate amounts of well-oxygenated blood at a pH close to 7.4. PGs and NO have important roles in these repair mechanisms Written by Dr Sebastian Zeki

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