FRS 1. Oesophageal anatomy, physiology, and pharmacology. Acid secretion Flashcards

Question

Describe the lifestyle changes adopted in the management of GORD

Answer 1

 Weight loss  Elevate head of bed at night  Avoid precipitants, e.g. coffee, chocolate, tomatoes, alcohol, and fatty or spicy food

Answer 2

- PPIs - H2 receptor antagonsists - antacids - alginates - mucosal agents - prokinetics

Answer 3

Proton-pump inhibitors (mainstay of therapy)

Answer 4

 Accumulate selectively in the canaliculi of the parietal cells  Undergo an acid-catalysed rearrangement to the active drug  This cationic sulfenamide binds irreversibly with sulphydryl groups on the proton pump causing inhibition  Irreversible inhibition leads to longer duration of action compared to H2RAs

Answer 5

``` o Diarrhoea (esp. Lansoprazole) o Rash o Headache o Infections – C. diff o Interact with cytochrome P450 - Clopidogrel (?Pantoprazole) o Long-term use - ?GNETs ```

Answer 6

Competitively block histamine receptors on the | parietal cell

Answer 7

``` o Diarrhoea o Deranged LFTs o Headache o Dizziness o Fatigue o Rash ``` Tachyphylaxis

Answer 8

a rapid decrease in the response to a drug due to previous (long term) exposure to that drug

Answer 9

o Cimetidine o Ranitidine o Famotidine o Nizatidine

Answer 10

o Raise the pH of gastric secretions o Decrease pepsin activity o Some bind bile acids o Duration of action depends on rate of gastric emptying

Answer 11

predominantly aluminium and magnesium salts => neutralise the effects of stomach acid

Answer 12

o Al salts – constipation o Mg salts – diarrhoea o Some formulations have high Na levels – avoid in cardiac/renal disease o Interact with tetracyclines, digoxin, iron, prednisilone.

Answer 13

 Giant Pacific Kelp - Macrocystis pyrifera o Algin extracted  Sodium alginate used in treatment of GORD  Mixture of polyurionic acids  Added to antacid preparations as foaming agents  Layer of foam on stomach contents – mechanical barrier to reflux.

Answer 14

 Metoclopramide/domperidone  Both increase gastric emptying and increase LOS pressure  Metoclopramide also acts on cholinergic systems in GI tract to increase ACh release  Useful GORD and functional dyspepsia o Early satiety, belching, nausea +/or bloating

Answer 15

drowsiness, diarrhoea, hyperprolactinaemia

Answer 16

 Complex sucrose polymer, cytoprotective agent o sucrose sulfate-aluminium complex o Binds to the ulcer, creating a physical barrier that protects the gastrointestinal tract from stomach acid and prevents the degradation of mucus o Anionic sulphate binds to positively charged glycoproteins in ulcer  Forms a ‘paste’, impeding diffusion of acid and acting as buffer for 6-8 hours

Answer 17

 Repair of hiatal hernia, if one is present. o Involves tightening the opening in the diaphragm with stitches  Laparoscopic Nissen fundoplication o Wrapping the fundus of the stomach around the end of the oesophagus with stitches. o The stitches create pressure at the end of the oesophagus, reinforcing the lower oesophageal sphincter o This helps prevent stomach acid and food from flowing up from the stomach into the oesophagus.

Answer 18

 Iron deficiency anaemia (may indicate bleeding)  Unintentional weight loss  Dysphagia  Persistent vomiting  Epigastric mass  >55 with unexplained and persistent dyspepsia

Answer 19

1. chronic inflammation of fundic glands 2. parietal cell atrophy 3. resulting in reduced acid secretion (hypochlorhydria or achlorhydria) 4. => increased gastrin production

Answer 20

 Can be performed with topical anaesthesia or conscious sedation  Direct visualisation of upper GI tract to d2  Diagnosis of structural and mucosal abnormalities, e.g. Hiatus hernia, tumours, Barrett’s oesophagus  Allows mucosal biopsy  Therapeutic intervention  Complications

Answer 21

 Used to remove tissue affected by Barrett’s oesophagus |  Endoscopic technique in which diseased tissue is exposed to heat energy and destroyed

Answer 22

Oesophageal pH monitoring

Answer 23

 Provides direct physiologic measurement of acid in the oesophagus and is the most objective method to o document reflux disease o assess the severity of the disease o monitor the response of the disease to medical or surgical treatment

Answer 24

 the sensor is placed 5 cm above upper border of the lower oesophageal sphincter (LOS) determined by oesophageal manometry.  To measure proximal oesophageal acid exposure the second sensor is placed 1-5 below the lower border of the upper oesophageal sphincter (UOS).  Oesophageal pH monitoring is performed for 24 or 48 hours and at the end of recording, a patients tracing is analysed and the results are expressed using six standard components.  Of these 6 parameters, a pH score called a DeMeester Score is been calculated o This is a global measure of oesophageal acid exposure. o A Demeester score > 14.72 indicates reflux.

Answer 25

A reflux episode is defined as oesophageal pH drop below 4 | o pH below 4 is damaging because pepsin is active at pH 4

Answer 26

Normal pH trace would show relatively constant pH around 7 with a few short dips in the day Abnormal: o Episodes of change in pH are more frequent and more prolonged

Answer 27

 Allows recording of pressures within the oesophagus and proximal stomach.  Oesophageal manometry measures the rhythmic muscle contractions that occur in your oesophagus when you swallow  assesses motility  Oesophageal manometry also measures the coordination and force exerted by the muscles of your oesophagus

Answer 28

 Catheter inserted through nose with local anaesthetic spray.  Display showing pressures as colour plot or lines  Diagnosis of motility disorders eg oesophageal spasm,

Answer 29

 An electrode mounted on a balloon catheter or an endoscope is used to deliver heat energy directly to the diseased lining of the oesophagus  Tissue sloughs off over 48 to72 hours following the procedure.  Over a period of six to eight weeks, this tissue is replaced by normal (squamous) lining

Answer 30

(Black blood) = partially digested, therefore it must originate from the upper GI tract and have been mixed with acid

Answer 31

o Gastric body contains oxyntic glands  Contains parietal cells that secrete HCl and INTRINSIC FACTOR o Gastric antrum contains pyloric glands  Contain G cells that secrete GASTRIN

Answer 32

 Acetylcholine (neuronal – parasympathetic)  Gastrin (G cell – endocrine)  Histamine (ECL cell – paracrine)  Somatostatin (D cell – endocrine)

Answer 33

 ACh acts on parietal cells  ACh acts on G cells to increase gastrin secretion  this increases acid production by stimulating parietal cell via CCK2 o Stimulates ECL cells to secrete histamine  these act on H2 receptors on parietal cells, increasing acid secretion  ACh inhibits D cells, inhibiting somatostatin production (inhibits the inhibitor)

Answer 34

 When food is ingested, proteins in food buffer acid, increasing the pH in the stomach  Gastrin is produced in response to elevated pH, stimulating increased acid production  More acid is produced in response

Answer 35

 When food leaves the stomach, gastric pH drops  D cells secrete somatostatin in response, which inhibits acid production  Acid secretion falls

Answer 36

 Kills bacteria  Denatures proteins  Aids in absorption of iron, vitamin B12 and calcium o Calcium is oxidised from Ca 2+ to Ca 3+ to assist in absorption

Answer 37

prostaglandins

Answer 38

Arachidonic acid pathway o AA is broken down into prostaglandins by COX-1 (constitutive) o COX-2 (inducible) is responsible for inflammatory effects  PGI 2 and PGE

Answer 39

NSAIDs cause peptic ulceration because they are non-selective COX inhibitors However, selective COX-2 inhibitors have been unsuccessful and were withdrawn from the market because of cardiovascular toxicity

Answer 40

imbalance between attack (acid) and defence

Answer 41

o Zollinger Ellison Syndrome (gastrin producing tumour)  Can be controlled with antisecretory drugs o Helicobacter pylori antral gastritis

Answer 42

o NSAIDs o “Stress” ulceration (e.g. following major trauma or burns)  less COX-1 action because of excessvie COX-2 action  reduced by nasogastric feeding and antisecretory drugs o H pylori infection corpus/pan gastritis

Answer 43

 Erosion into blood vessel  Perforated peptic ulcer  erosion through outside wall of stomach or duodenum causes acute leak of gastric contents or air into peritonitis o Acute pan-abdominal pain  Anaemia – tired and breathless, pale conjunctiva

Answer 44

High urease activity => catalyses the reaction between urea and water to form ammonia

Answer 45

o Now mostly colonises the antrum and not the body o This decreases somatostatin production, increases gastrin production  increased overall acid secretion (hypersecretion) o Mucous protection layer is less effective o Prone to duodenal ulcers and ulcers in the pre-pyloric region o Slight protective effect against gastric and duodenal cancers o Treat, usually no need for repeat endoscopies

Answer 46

dominates in the East (Japan etc.) o Pan gastritis o Parietal cells and oxyntic glands are inflamed =>decreased acid production o Inflammation wears away the gastric defence, leaving people at risk of ulcers and gastric cancer o Stomach becomes colonised by other bacteria (due to hyposecretion of acid) o Repeat endoscopies

Answer 47

1. blood test 2. stool test 3. breath test 4. endoscopy

Answer 48

serology for h pylori antibodies NB: will always be positive even after infection has cleared. Therefore useful for primary investigation only, not follow-up after treatment

Answer 49

test for bacteria antigen

Answer 50

– urea breath test - patient given urea that is labelled with C 13 /C 14 - then asked to breathe out into bag to determine how much of the exhaled carbon is labelled - no helicobacter, urea will be absorbed and urinated out, only C 12 in breath test - positive test will show heavier carbon isotope in exhaled air

Answer 51

test urease activity on gastric biopsy, or microscopic analysis (histological biopsy) - rapid urease test (contains pH indicator). Production of ammonia changes colour from yellow to red

Answer 52

The low pH in the stomach converts all of the PPI to the ionised form, which cannot be absorbed. It therefore has to be packaged in enteric coating  It is absorbed in the small intestine and is transported to parietal cells o Here is becomes ionised and is trapped within the parietal cells o PPI forms an unbreakable disulphide bond with the proton pump, blocking it

Answer 53

 Can’t heal an ulcer/eradicate H pylori without reducing acid secretion  The pH need to be > 4 for extended period of time to allow for the stomach/duodenum to heal

FRS 1. Oesophageal anatomy, physiology, and pharmacology. Acid secretion Flashcards

(77 cards)