3.2 Peptic Ulceration

• in small intestines - ideal as large SA due to microvilli
• pancreas produces enzyme rich secretion and aqueous alkaline secretion:
  • HCO3- exchanged with CL
  • Cl- ion channel absent in people with CF, can cause malabsorption
  • glands have acinar cells which produce lots of enzymes
  • enzymes modifyed by HCO3- which is exchanged with Cl-
• function of bicarbnonate --> neutralise acid chyme ready for 
  • digestive enzyme activity
  • micelle formation (fat absorption)  --> emulsify the fat, helps transport the fats, works best at neutral pH
  • protecting duodenal mucosa --> if acid gets into duodenum can get ulcers
• 

• ingested as complex carbohydrate --> startch (plants), Glycogen (meat)
• digestion begins in mouth (salivary a-amylase), ceases in acidic enviroment of stomach
• most carb digestion in SI by pancreatic a-amylase
  • acts on a-1,4 glycosidic bonds
• subsequent digestion by enzymes located on brush border
  • closely associated with Na cotransporters- transfer monosaccharides from lumen to blood
  • transported across membrane by creating N concentration gradient
    • Na pumps in vasoatra side, use ATP to pump from inside to outside
    • Na conc in cell decreases, turns on pump near lumen and activates associated enzymes which acts on disaccharidse and transports into cell
    • monosacchardides pass into capillaries to supply mesentery
• 

• begins in stomach (pepsin) ~15% activity halted by alkaline pancreatic secretions
• once chyme enters SI HCO3- neutralises pepsin
• 2 main classes of pancreatic enzymes responsible for protein digestion
  • endopeptidases - cleave interior peptide bonds
  • exopeptidases - cleave external peptide bonds
• secreted into duodenum as in active precursor (prevents autodigestion), activated by trypsin
• 
  • trypsin in brush border
  • trypsin breaks down proteins which turns inactive enzyme to active enzyme
  • activated enzymes break down aa in chyme
• further digestion occurs further action of peptiases located on brush borreder
  • will still absorb proteins if pancreas damaged
• abdorbtion of aa and di + tri prptides occurs by passive diffusion or facillitated transport
  • di and tripeptides broken down to aa by intracellulear peptidases

• pancreatic lipase is fat soluble- therefore to access lipid site require emulsification of lipid droplets ton increase SA of lipid water layer
• emulsification involes bile acids, derived from liver + released from stores in gall bladderLipase takes off FA to produce monoglyceride and free FA
  • bile salts have lipid soluble head and negatively charged tail (H2O soluble)
  • breaks fat down into smaller units so greater area for pancreatic lipase can digest fat
• Diffuse easily into capillaries but most stay as FA and glycerolproducts from action of pancreatic lipase - monosaccharides and FFA (and some glycerol), not h2o soluble, absorbed by forming micelle
  • duodenum has water layer, so needs to be water solube
  • bile salts form micelles, tails stick out so more H2O soluble
  • micelle goes past h2o layer and releases contents into cells and reform triglyceride
  • transported round body by joining protein , monosaccharide and cholesterol to form chylomicron so more H2O soluble
    • chylomicron too big for capillaries so pass into lymphatic system
• intracellular reformation of triglyceride, combine with phospholipids, cholesterol and protein to form chylomicron, transported via lymphatic system

• Vagus Nerve
  • conditioned stimuli (cephalic phase) --> prepared response before food arrives in SI
  • prescense of food in stomach is gastric phase
• ACh acts to potenate actions of secretin and cholecystokinin (CCK)
  • released from acinar cells in pancreas
  • secretin (released from response of acid in duodenum) stimulates HCO3- production
  • CCK stimulates enzyme rich secretion 
    • released in response to prescense of fat and protein in duodenum
• somatostain inhibits pancreatic secretions
• 

• Gluten enteropathy 
  • gluten in diet cause mucosal damage 
  • decrease villi SA for absorption
  • increased delivery of nutrients to arge intestine producing diarrhoea (osmaotic) and flatulence
  • Treatment - gluten free diet
• gluten induced autoimmune disease
• steatorrhea, fatigue (anaemia), Weight loss or failure to thrive in children

• Acute - autodigestion of pancreas by secreted enzymes
  • can be due to blockage of pancreatic duct caused by bile duct stones
• Chronic - normally associated with alcohol abuse
• Symptoms incude steatorrhea (fatty stools) due to fat malabsorption (lack of pancreatic lipase), and diabetes (lack of insulin)
• no major effect on carbohydrate and protein digestion due to presence of additional digestive enzyme in SI

• arond 1L produced each day
  • resting flow rate --> 0.5 ml/min
  • maximal flow rate --> 7ml/min
• saliva production is protective if about to vomit
• 
• Acinar Cells- Produce primary secretion that;s isotonic with plasma, some salivary proteins secreted
  • closed end of gland is acinar
• Duct Cells - ctively reabsorb Na+ (& Cl-), some secretion of K+ and HCO3-, impermable to h20, excess absorption means saliva is hypotonic relative to plasma
• Myocytes - have contractile functionand help push products up past duct cell which modify the primary secretion (mainly absorbing ions)

• composition isn't always constant --> depends on rate of flow
  • electrolyte flow changes
• when production is slow, lots of Na+ and Cl- reabsorbed
• duct cells will secrete K+ into saliva
• Na+ conc increases as flow rate increass, so in contact with duct cells less, so less time to reabsorb  (same for Cl-)
• less K + secretion as flow rate increases as less time
• HCO3- increases
• saliva also contains
  • mucous
  • proteins (incuding IgA)
  • enzymes (e.g. amylase, lysozyme)

• secretion id under neural control
• both parasympathetic and sympathetic can be activated in response to certain stimuli
• 
• eating, chewing or smelling food activate chemorecptor and pressure and send signals to salivary glands which cause secretion
• parasympathetic stimulation of acinar cells produce large vol of serous saliva rich in enzymes
• alteration in blood flow essential to increases salivary secretion
• Kallikrein activates protein that flows in plasma forming peptide hormone bradykinin, causes local vasodilation of arteries and makes capillaries leakier so more fluid can move out and move between acinar cells to increase saliva production
• sympathetic nerve action produces small volume of thick saliva rich in mucous,
  • cause local vasodilation and less leaky

• contains salivary amylase --> starts breakdown of polysaccharides (15% carb digestion)
  • not much digestion of fats and proteins in mouth
• produces mucous --> facillitates swallowing
  • no sharp edges down, smooth passage
• protective function --> facilitates swallowing
  • also secretes lysozyme (antibacterial), IgA
• act as solvent to stimulate taste
• moisturiser --> aids speech
• promote oral hygeine
• contains bicarbonate --> neutralises acids in food to reduce dental cavities
  • actively secreted when begin salvating more
  • help neutralise vomit

• Inihiated when food bolus is forced by tongue to rear of mouth to pharynx
• 2 phases
  • Oropharyngeal --> food bolus is directed into oesophagus (requires sealing off nasal passage by uvula and trachea b glottis
  • Oesophageal --> oesophagus is protected from damage caused by passing food bolus by mucous secretion, movement by peristalsis 
    • above bolus SM is contracted and below is relaxed
• food then passes to stomach
  • top part able to store without receptive relaxation
  • bottom bit allows movement out
• 

• Hindgut enter endoderm lined cavity called cloaca
• cloaca is endoderm lined cavity in close proximity to overlying ectoderm, when close is cloacal membrane
• As development continues urorectal septum arises between the cloaca and allantois
  • Starts to grow down caudally
• At week 7, cloaca has been separated, urorectal septum has gone down to fuse with cloacal membrane which at that point is the perineum
• Separates one membrane into 2: urogenital (blue, anterior) and anal membrane (yellow, posterior)
• At week 9 anal membrane with rupture and there will be a free communication into extra embryonic surroindings
• Blue gives rise to bladder and urethra, Urogenital sinus (blue)
• Urinary bladder – the largest bit b) Narrow canal -  pelvic part, urethra c) Definitive urogenital sinus – differs in male and female
• 

• epithelium endothelium derived
• surrounding structures of urethra from splanchnic mesoderm (muscle and connective tissue)
• urethra longer in male
• at 3rd month epithelium at proxima part of urethra whill start budding out (more in males), pushes into mesoderm and mesenchyme surrounding it
  • will give rise to prostate gland in male
  • in female have glands in similar area called urethral and paraurethral glands

• abnorma passageway or duct betweem 2 structures that would not normally have that communication
• in hindgut usually associated with rectum
• between:
  • Rectum and Vagina --> rectovaginal fistula
  • Rectum and bladder --> rectovesical fistula
  • Rectum and Urethra --> urorectal fistula
• formed by deviation by urorectal septum, hasn't made it down to cloacial membrane
• rectal fistulas frequently observed in association with an imperforate anus (where anal membrane persists)

• 3 major stages --> 1st  2 transient (week 4)
  • Pronephros - intermediate mesoderm strat to dissociate from somites and form cell clusters called nephrotomes (1st kidney system to develop)
  • Mesonephros - unsegmented mesoderm gives rise to 2nd kidney system and is semi-functiioning, mesonephric duct important in kidney development and reproductive tract runs along it
• 3rd part persists as functioning kidney
  • Metanephros - starts as outbudding of mesenephric duct, mesonephric duct enters developing bladder in ventral and lateral part by ureteric bud which will become ureter, outbudding starts to be surrounded by metanephric covering of mesoderm associated cells

• Ureteric bud - ureter, renal pelvis, major and minor calyses, 1-3 million collecting tubelles - collecting system
• Mesanephric mesoderm - excretory units
• Ureteric bud elongates
• expanding area is renal pelvis, expanding part of top of ureter
• bud will continue to grow and split into major calyx ehich splits into minor calyx
• continues to split and have collecting tubelles

• kidney need to ascent during development
• reduction in body curvature, more proliferation takes place in saral and lumber regions , as a result kidneys will ascend
• recieves blood supply from aorta, as rises get it from higher level and lower obliterates until high up renal artery

• ovaries in female, male in testis
• gondal ridges on either side of midine near mesonephros
• germ cells located between endoderm epitheium in wall of yolk sac at point of allontois and migrate along dorsal mesentery to genital ridges
  • if germ cells don't get there then gonads don't develop
• genital ridges proliferate as germ cells come towards them - week 5/6

• black are genital ridges, red proliferating epithelium
• epithelium proliferate, germ cells come round, epithelial cells surround them and form cortical cord
• cells break down and start to get cell clusters
• germ cells are oocytes which are surrounded by epithelial follicular cells
• paramesonephric duct important in female reproduction system as fuse in midline

• paramesonephric duct on either side and are in close contact in midline
• fuse in midline to form uterus and fallopian tube and upper part of vagina
• germ cells in ovaries
• cords in male reatin solid until puberty when lumen will form
• in male mesonephric duct is important in male reproductive duct in ductus defrens and epididymis
• paramesonephric duct disintergrates in male

• epithelium proliferate as germ cells move
• cords formed by germ cells
• cords dissociate from overlying epithelium --> tunica albuginea  (white structure)

• female ovaries descend into pelvis region --> less extensive
• gubernaculum on posterior side of testis, condensation of mesenchyme & rich in ECM proteins and help guide testis
• descent of testis occupies position in scrotum, at time of birth by going down inguinal region
  • come down inferior part of abdomen, need to get to scrotal region by going through inguinal region which has inguinal canal as it does takes covering of peritoneum now called tunica vaginalis, in scrotal sac

• connection with peritoneal cavity should be obliterated
• can be left open, there is open communication with abdomen and bowel can come down and cause indirect inguinal hernia

• either sides folds start to form and unite to form genital tubercle,
• either side genital swellings
  • these swellings form mesenchyme
  • anteriorly unite to form genital tubercle
  • urorectal septum breaks cloacal membrane up into anterior and posterior membrane
  • 7 weeks
• perineum formed

• release of androgens from developing testis and signal tissues to elongate (tubercle)
• urethral folds will elongate and fuse in midline to form developing penis
• scrotal sac swellings will continue to grow to form scrotum

• No androgens as there is no testis
• genital tubercle will elongate to form clitor-is
• urethral folds won't fuse and will be labia minora
• swellings won't fuse and become labia majora

• commonist cause of end stage renal failure in young children
• renal agenesis (absence of kidney) & dysplasia (prescene but misformed)
• ectopic kodney (not on right place, doesn't work)
• Horseshoe kidney (kidneys fused together and ascend stopped by aorta and SM vessels)
• Double ureter
• bladder exstrophy (bladder exposed)
• Vestcoureteral reflux (VUR) --> retrograde flow of urine from bladder to kidney
• 

• Paramesonephric ducts
  • lack of fusion --> uterus bicornes
  • Complete/partial atresia --> atresia of cervix and vagina, urethral folds
  • Incomplete fusion --> hypospadias
• disorder of sec development (DSD)
• Sex chromosome DSD --> klinefelters syndrome (47, XXY), Turners syndrome ($%, X)

• mucosa changes alot throughout
• submucosa --> contains big blood vessels, lymphatic drainage immune cells
• muscle has 2 layers
• Wrapping/Adventitia --> connective tissue (collagen) wrapping to seperate from organ
• some areas have serosa --> single layer of squamous epithelial cells and produce a small amount of serous fluid so gut can slip and slide over each other

Consists of:

• epithelium - changes throughout tube in relation to function
• basement membrane --> where epithelium lies
• laminal propria --> supports epithelium (structurally and nutritionally), under basement membrane
  • connective tissue enables mechanical support
• muscularis muscoa --> cause lining to be visably folded
  • has little muscle to be allowed to be folded to give extra SA

• if want to secrete more, then have more glands, generally columnar, ducts cuboidal
• if want more absorption then more folding
• squamous good for diffusion
• Protective - oral cavity and pharynx, oesophagus, anal canal, stratified squamous non-keratinising
• Secretory - stomach: simple/branched tubular glands for acid secretion, columnar is good for secretion
• Absorptive - SI projections (villi) and glands (crypts) lined by columnarcells (enterocytes) specialised for absorption (microvilli), goblet cells produce mucous for lubrication and protection
• Protective - large intestine, lots of goblet cells for lubrication of faeces, enterocytes absorb water, columnar with villi

Consists of:

• connective tissue, blood vessels, lymphatics and nerves
• some of the glands
• submucosal (Meissner's) plexus --> supplies glands and muscularis mucosa

• Consists of:
• Smooth muscle (externa): inner circular and outer longitudinal. Responsible for movement of food along the gut tube: peristalsis. 
• Modulated by the autonomic nervous system: Myenteric (Auerbach’s) plexus between muscle layers modulates peristalsis

Moves at a fairly consistent rate except when have issues like IBS or infection, or may slow down if not enough fibre or there is an obstruction

• sphincters are thickening of SM
• oesophageogastric --> prevents reflux of stomach contents
  • if too much reflux epithelium changes to more stomach epithelium - metaplasia, barrets oesophagus
  • increases risk of cancer
• Pyloric --> between stomach and duodenum, controlled release of food
  • controlled release of acid as duodenum is alkaline so can neutralise it
• Ileocecal --> between small and large intestine
• Internal Anal --> upper anal canal - retains faeces

Mucosa

• epithelium --> lining is stratified squamous non-keratinising, masticatory surfaces (gingivae, hard palate, dorsum of tongue) ae slightly different (retain nuclei in upper layers, gives whitish colour)
• lamina propria
• no muscularis mucosa

Submucosa

• contains small salivary glands (origin adenocarcinoma)

Lips

• fold of skeletal muscle (orbicularis oris) covered by keratinised squamous w/o adnexal structures (absence of glands gives dry feeling) thick stratum amd high dermal papillae with rich capillaries

• 3 paired salivary glands --> all consist of lobules of acini and ducts, divided by connective tissue septa (intersrtium produces IgA)
• Parotid
  • secrete vias parotid duct
  • has connective tissue capsule
  • serous secretion
• submandibular
  • secretes by submandibular (Whartons) duct 
  • has connective tissue capsule
  • mixed muco-serous secretion
• sublinguinal
  • no capsule
  • mixed sero-mucous secretion

• bulk of interlaced bundles of skeletal muscles covered by oral epithelium 
• attached to floor of mouth
• mucosa of anterior dorsal surface has masticatory epithelium with tiny projections called papillae
• has lamina propria and muscle core w minor salivary glands and some fat
• circumvallate papillae have most taste buds

Taste Buds

• ~50-100 taste receptor cells form 1 taste bud
• long microvilli are present at apex of receptor cells
• taste buds only open to surface via taste pore
• sensory nerve fibres penetrate the base of taste bud

• 
  HCl produced by parietal cells
• carbonic anhydrase catalyses carbonic acid which dissociates into H+ and HCO3-
• H+ transported in by pump which exchanges with K+
• HCO3- transported back into plasma for Cl-
• Cl- transported into lumen. K+ using cotransport protein
• gastric lumen increase H+ and Cl- 
• K+ move in and out of lumen with Cl- and H+
• at pit of gastric mucosa pH= 0.8-1.0 = 160mmol/L

Aids digestion by

• activation pepsin and providing acid medium for optimal pepsin activity
  • aids breakdown if connective tissue and muscle fibres - proteins
• acid enviroment crucial as non-specific defence mechanism, killing ingested microorganisms
• denatures molecules you eat so easier to digest
• parietal cels also increase intrinsic factor that binds VitB12 to enable absorption

Pepinogen

• pepsinogen is produced by chief cells
• when acidic enviroment  some of molecule break downto smaller polypeptide pepsin
• pepsin will cleave large chains of amino acids causing peptode fragments
• autocatalytic enzyme --> pepsin will act on pepsinogen to produce more pepsin
• 

• gastric secretion stimulated prior to arriva of food in stomach
• stimulated by thought or expectation of foos and sight, taste, cheing or swallowing food
• contributes significantly to gastric secretion in man (30%-50%)
• dependant upon activity of vagus nerve

• recieves innervationfrom parasympathetic which releases ACh which acts in muscarinic recptor which releases HCl
• Enterochromafin cells releases histamine and recieves parasympathetic innervation & activated by ACh to release histamine and cross space to interact w H2 receptor on parietal cell --> changes cAMP level which activates protein pump and HCl release
• Antral G Cells contain gastrin --. recieves parasympathetic innervation, innervated by peptide molecule GRP (gastrin releasing peptide), causes gastrin released into local circulatory system and acts as circulating hormone, goes to enterochromaffin cel to release more histamine, stimulates more H2 receptor so bigger HCl release, CCK-2 cells on parietal cell activated by gastrin to release more HCL
• D- Cells contain stomato-statin (**) acts to decrease HC production by inhibiting gastrin release, parasympathetic decreases activity
• all happens before food arrives into stomach

• Increasing blood flow during digestion is vital
• share of cardiac output
  • resting stomach --> 0.5%
  • Active stomach --> >10%
• Mechanisms
  • local metabolite production production (prostaglandins maintain capillary network)
  • may be release of vasoactive intestinal polypeptide (VIP) from local nerves causing vasodilation

as meal gradually passed to SI, gastric secretions are reduced due to:

• removal of peptide fragments -- no longer present to stimulate gastrin release
• Removal of food leads to decrease in pH--> at pH less than 2, gastrin release from G-cells is inhibited directly and via somatostatin release
• distension of duodenum or prescense of acid or food products in chyme, leads to release of 'enterogastrone' (mixture of hormones including cholecystkinin from duodenal wall), which inhibits gastrin release, either directly or via somatostatin release
• gastric secretion can also be influenced by cephalic factors such as fear or depression

• stomach frequently contains concentrated HCl and proteolytic enzymes
• mechanisms incude:
  • luminal membranes of gastric mucosal cells are impermable to H+ ions
  • cells interconnected with tight junctions, therefore no H+ movement between cells
  • negative feedback, pH <2.0 inhibits G-cells directly and via somtostatin release from D-cells
  • mucous released from surface epithelial cells
  • 
• rapid repair of damaged mucosa (cell lining stomach turnover - 3 days)
• secrete HCO3- from vascular and prostaglandins maintain vasolation to have neutral mucus

• Raw eggs
• Salmonella enteritidis
  • causes gastroeneteritis
  • grown using selective agar
  • gastroenteritis usually self limiting
  • symptoms can persist fpr days
• Salmonella Typhi and Paratyphi
  
  • cause typhoid or paratyphoid fever --> severe systemic illness
  • can be grown from blood cultures
  • give antibiotics (IV ceftriaxone)
  • can invade gut and enter blood stream
  • can cause bowel perforation, fluctuating fever

• anaerobic Spore FormerCan colonise w/o causing disease
  • spores survive and spread
  • germinate back into cells
  • vegetative cells produce toxin
• antibiotics kill other resident bacteria and let C.diff multiply to high numbers --> disease
• lots of c.diff can cause inflammation of gut --> can get perforation or need colectomy
• disease varies from diarrheoa to toxic megacolon and perforation
• Diagnosis
  • samples sent from hospital patients with diarrhoea
  • can check if colonised with C.diff by PCR
  • ELISA used to see if producing toxins
• Treatment
  • depends on severity
  • most effective orally
  • metronidazole - mild
  • vancomycin - mod/severe

• Bacterial infection
  • Chronic gastritis
  • Duodenal ulcer disease (80%)
  • Inflammatory response
  • Associated with gastric adenocarcinoma
• Epidemiology
  • 20-30% world’s population affected
  • Higher in developing world (70%)
  • Minority develop ulcers
• Diagnosis
  • Urease breath test
  • Endoscopy and gastric biopsy
  • Serology (antibody testing)
• Treatment
  • Combination of 2 antibiotics - Amoxicillin, Clarithromycin, Metronidazole, Tetracycline, Protein pump inhibitor

• capsule the drug doesn't get degraded before it acts
• if want it slow down absorption so acts over longer period of time
• in liquid is easier to get into blood
• type of preperation depends on how you want it to be absorbed
• some have pH dependant coating so releases drug at certai pH
• size of tablet determines how quickly absorbed --> small fragments easier to absorb

• formuated to resist dissolution
• can slow rate at which drug broken down
• EC --> wax coating drug so that there is less irratation on the stomach
• sustained release --> slower, more constatnt release, so longer action
• may be used to reduce rate of absorption and prolong action, deliver drug to specific region of GI Tract
• 

• e.g. glyceryl trinitrate and fentanyl
• applied as patches
  • formulated with ethanol to enhance skin penetration
• provides sustained release
• Fentanyl patches
  • might not be able to swallow
  • replace oral morphine
  • use equivalent doses 

• Stroke
  • review medication
  • may need to administer drugs via NG tube or IV
• Severe Infection
  • intravenous antibiotics
•  Pallative Care:
  • morphogesicno longer swallowed
  • swap to fentanyl patches
  • diamorphine via syringe driver

• Short-Acting
  • soluble rapid onset and short duration
• Immediate action
  • suspension with protamine
  • useful for twice daily regimen
• Long-Acting
  • large crystals, high zinc content
  • slow onset and long duration

• used to aid compliance with injections weekly/monthly 
• absorption by thick oils that slow down rate of diffusion from injection site
  • avoids first pass metabolism --> careful of bioequivalence
• noresthisterone enentate in oil (contraception)
  • 8 weeks
• Fluphenazine decanoate in oil (schizophrenia)
  • compliance
  • prolonged action (and side effects)

100% = 100g per 100ml or 1g per ml

10% = 10g per 100ml, 100mg per ml

1% = 1g per 100ml, 10mg per ml

0.1% = 100mg per 100mg, 1mg per ml

Ratios: Adrenaline

1:1000 = 1mg/ml

1:10,00 = 100 micrograms/ml

1:200,000 = 5 micrograms

• reflux of acidic stomach contents into oesophagus causing erosion damage - heart burn
• can be made worse if lean forward
• can be caused by obesity, pregnancy, drug induced
• causes by weak sphincter, relaxation of sphincter by drugs, increased intra-abdominal pressure - pregnancy and obesity
• peptic ulceration - erosioma, damage, bleeding (anaemia), acid starts to pour into wound causing pain, can lead to Fe deficient anaemia
• zollinger-ellison syndrome --> hypersecretion and hyperacidity
• Gastritis - inflammation of stomach
• Drud (NSAID and oral Steroids) induced damage  - adverse drug raction

• epigastric pain which may be precisly located by patient by pointing
  • pain variable in relation to food
• DU: hunger pain which is relieved by eating 
• night pain relieved by food, milk or antacids
• water brash --> nasty fluid in mouth
• nausea and less frequent vomiting
• vomiting blood - haematemesis

Warning signs

• aged over 55
• weight loss
• anaemia
• dysphagia
• haematemesis (vomiting blood)
• Melaena (tarry stools)
• upper abdominal masses
• persistant symptoms with repeat requests for OTC remedies

• Helicobacter pylori - 80-90% of patients w duodenal ulcer have this
• infection may lead to chronic inflammation and gastric damage (gastritis) leading to ulceration
• Tests for H.pylori - urea breath test (13C urea), biopsy for urease activity, H.pylori antigens/antibodies in blood, saliva, stools
• give urea withh 13C, H.pyori produced urease which breaks down urea, HH3 neutralises can survive
• labelled urea broken down, and heave CO2 released into blood and breath can be detected
• 

• increase acid secretion by histamine via H2 receptors, gsatrin, acetylcholine vis M-receptors, M3 on parietal cells
• decrease acid secretion by prostaglandins (E2 and I2), cytoprotective via HCO3- and mucus release
• ACh acts as muscarinic by the Ca activating protein pump
• ECF stimulated by ACh and releases histamine & acts at H2 receptor, uses cAMP in cell for pump
• gastrin stimulates CCK2 receptor, uses Ca inside cell, stimulates protein pump, pumps out H+ for K
• prostaglandins receptor inhibit the pump

• sympotomatic relief or cure
• may involve lifestyle changes
  • avoidnace of causative drugs
  • avoidnace of causative 
  • GORD - propping bed, removing belts
• suppression of acid release to allow natural healing and if appropriate, eradication of H.pylori infection
  • reduces chance of developing gastric carcinomas, as pylori is regarded as a carciinogen

• Antacids - are anti-acid, available over the counter (OTC) and raise pH
  • provide rapid relief but are not the cure
  • HCO3- the most simple
    •  HCO₃^-+ H⁺        à         CO₂+ H₂0
  • Magnesium hydroxide also used
    • Mg(OH)₂    + 2HCl      à       MgCl₂  + 2H₂O
  • Ca Salts - gastrin release in the long term

• main ones ranitidine (tagament), famotidine (pepcid)
• Low dose OTC for short term relief, high dose POM
• competiive antagonist for H2 receptor so less stimulation, only take out 1 pathway
• H2 receptors coupled vis adenylyl cyclase to increase cAMP activating proton pump
• reduce gastric acid secretion
• provide symptomatic relief
• best given at night
• promote ulcer healing (relapse on discontinuation)
• reduces the need for surgery
• H1 receptor antagonists are 'antihistamines'
• cimetidine - inhibits cytochrome P450 and therefor ethe metabolism of other drugs causing drung interaction w oral antioagulants, phenytoin, carbamazepine, tricyclic antidepressant
• rantidine doesnt always act this way

• e.g. omeprazole, esomeprazole, pantoprazole, lansoprazole
• irreversible inhibition of proton pump --> H+/K+-ATPase
• activated by acidic pH
• enters the body and passes to parietal cells, the pKa means it is activated at low ph, this localises the action the drug

Adverse Effects

• inhibits H+ secretion by >90%, may lead ro achlorhydria
• increase risk of campylobacter infection

• eradication most effective treatment for long term cure of ulcer with low relapse rates
• variety of comination therapies --> "Triple Therapy"
• all involve antibiotics
  • 2 from 
    • clarithromycin --> has few drug interactions
    • amoxixillin --> avoid allergic to peicillin
    • metronidazole --> no alcohol
• also need one of
  • PPI and/or H2 antagonist
  • triple therapy for 1 week then PPI

Non-H.pylori Dyspepsia

• give PPI/H2RA as approiate

• prostaglandins incraese mucus, increase HCO3- and help protect stomach
• NSAIDS stop this by inhibiting COX pathway, so less protection of stomch and more acid produced, so more likely to get ulcer

• prophylaxis with PPI
• H2 antagonists less or in effective --> famotidine has been shown to be less effective
• give in combination with misoprostol - stable PGE1 analogue, acts on prostanoid receptors to inhibit gastric H+ secretion
  • can't use use in female patient of child bearing age as can cause abortions
• taking with food doesn't prevent ulceration, stops irration
• paracetamol isn't an NSAID