gastrointestinal_week_3_20190518174140 Flashcards
what causes oral cancer
tobacco and alcohol, HPV, candida
what diet factors cause cancer
low in vitamin A, C and iron - causes atrophy of oral mucosa which makes it more susceptible to local carcinogens
how is oral sex tied to cancer
HPV 16 and 18associated with oropharyngeal cancer
what is high risk sites for oral cancer
soft sites eg ventral tongue/floor of mouth and lateral tongue
what are potentially malignant lesions which can occur in mouth
erythroplaskia, arythroleukoplakia, leukoplakia, erosive lichen planus, submucous fibrosis, dyskeratonsis congenita
what is the warning signs for oral cancer
red and white lesion, ulcer, numb feeling, unexplained pain in mouth or neck, change in voice, dysphagia
what are other orofacial manifestations of cancer
drooping eye lid or facial palsy, fracture of mandible, double vision, blocked or bleeding from nose, facial swelling
what is DMF index
sum of decayed, missing or filled teeth of surfaces
what is def
a count of all primary teeth that are decayed, extracted due to caries or filled
what is DMFS
a count of all decayed or missing or filled tooth surfaces
what diseases can be characterised by inflammation of peridontal tissues
gangivitis, peridonitis, necrotising ulcerative gingivitis, peridontal abscess, perio-endo lesion, gingival enlargement
what can endoscopes visually diagnose
oesophagitis, gastritis, ulceration, coeliac disease, crohns disease, ulcerative colitis, sclerosing cholangitis
which vascular abnormalities can it detect
varices, ectatic blood vessels (GAVE, dieulafoy) and angiopsyplasia (small vessels)
which miscellaneous conditions can it detect
mallory-weiss tears, diverticulae, foreign bodies, stones, worms
what is able to be treated down endoscope
GI bleeding, nerve blocks, resection of early cancer
how is variecal bleeding treated
ABCinjection sclerotherapy (ethanolamine)banding histocryl glue
what is component of ingested lipids
fats/oils, phospholipids, cholesterol and cholesterol esters and fatty acids
what is the solubility properties of lipids
either insoluble (cholesterol esters) or poorly soluble (causing special problems for digestion and absorption - triacylglycerols and cholesterol)
lipids must be converted from solid fat an oil masses into an emulsion of small oil droplets suspended in water. How does emulsification occur
mouth - chewing stomach - gastric churning and squirting through the narrow pylorus - content mixed with digestive enzymes from mouth to stomach SI - segmentation and peristalsis mix luminal content with pancreatic and biliary secretions
how are emulsion droplets stabilised
addition of coat of amphiphilic molecules that form surface layer on droplets that include:product of lipid digestion (fatty acids, monoacylglycerols)biliary phospholipids cholesterolbile salts (when droplets have progressively been reduced to unilamellar and mixed micelles)
how does lipid digestion of TAG by enzymes (triacylglycerols - fat)
mouth - lingual phasestomach - gastric phase - by gastric lipase - resistant to digestion by pepsin (and lingual lipase in salvia)duodenum - intestinal phase - by pancreatic TAG lipase (produces 2-monoacylgylcerol and free fatty acids
how are bile salts released into duodenum
released in bile from the gall bladder in response to CCKThey act as detergents to help emulsify large lipid droplets to small droplets
what does failure to secrete bile salts result in
lipid malabsorption - steatorrhoea (fat in faeces)secondary vitamin deficiency due to failure to absorb fat soluble vitamins (A, D, E and K)
what is the downside to bile salts
they increase SA for attack by pancreatic lipasethis problem solved by colipase
how are free fatty acids and monoglycerides absorbed
transfer between mixed micelles and the apical membrane of enterocyte entering the cell by passive diffusion
what happens to short and medium chain fatty acids once absorbed
diffuse through enterocyte, exit through basolateral membrane and enter the villus capillaries
what happens to long chain fatty acids and monoglycerides once absorbed
resynthesised to triglycerides in endoplasmic reticulum and are subsequently incorporated into chylomicrons
how is cholesterol absorbed
mainly due to transport by endocytosis in clatherin coated pits by Niemann-Pick C1-like 1 (NPC1L1) protein ezetimibe binds to NPC1L1 so prevents cholesterol absorpton
what is acute oesophagitis (rare)
corrosive following chemical ingestion infective in immunocompromised patients eg candidiasis, herpes, CMV
what is chronic oesophagitis (common)
reflux disease (reflux oesophagitis)rare causes include crohns disease
what is definition of reflux oesophagitis
inflammation of oesophagus due to refluxed low pH gastric content
what is potential causes of reflux oesophagitis
defective sphincter mechanism abnormal oesophageal motility increased intraabdominal pressure (pregnancy)
what does reflux oesophagitis look like under microscope
basal zone epithelial expansion intraepithelial neutrophils, lymphocytes and eosinophils
what are the complications of reflux
ulceration (bleeding)stricture barretts oesophagus - replacement of stratified squamous epithelium by columnar epithelium
what is barretts oesophagus look like macroscopically
red velvety mucosa in lower oesophagus
what does barretts oesophagus look like microscopically
columnar lined mucosa with intestinal metaplasiaincreased risk of developing dysplasia and carcinoma
what is allergic oesophagitis (eosinophilic oesophagitis)
not due to reflux - increased eosinophils in blood corrugated or spotty oesophagus asthma, young, males > females
what is treatment for allergic oesophagitis
steroids, chromoglycate, montelukast
what is most common benign oesophageal tumour
squamous papilloma
what are common malignant tumours of oesophagus
squamous cell carcinoma and adenocarcinoma (now most common)
what is the pathogenesis of adenocarcinoma
genetic factors, reflux or others - chronic reflux oesophagitis - barretts oesophagus, low grade dysplasia - high grade - adenocarcinoma
what is the different mechanisms of metastases
direct invasion, lymphatic permeation, vascular invasion
what is most common oral cancer
squamous cell carcinoma
what is the characteristics of GORD
incompetent LOS, poor oesophageal clearance, barrier function/visceral sensitivity
what are the symptoms of GORD
heartburn, acid reflux, waterbrash, dysphagia, odynophagia, weight loss, chest pain, hoarseness, coughing
what investigations are involved in GORD
endoscopy, barium swallow test, oesophageal manometry & pH studies, nuclear studies
what are the alarming symptoms of dyspepsia (indigestion)
dysphagia, weight loss, anaemia, vomiting, UGI cancer, barretts, pernicious anaemia, PUD surgery > 20 years
what is the management of GORD
symptom relief, healing oesophagitis, prevent complications
what are the lifestyle modifications which help GORD
stop smoking, lose weight if obese, prop up the bed head, avoid provoking factors
what is the role of antacids in GORD
symptomatic relief in the majority of reflux patients no benefit in healing or preventing complications
H2 antagonists can also be used for symptomatic relief. What are examples of these drugs
cimetidine (rapid symptom relief, less effective at healing than placebo)ranitidine (tolerance after 4/52 therapy, poor in preventing relapse and complications)
what is the role of surgery (nissen fundoplication) in GORD
controls symptoms, heals oesophagitis, young patients, severe/unresponsive disease
what is barretts oesophagus
complication intestinal metaplasia irreversibleincreased risk of adenocarcinoma
what is the treatment for dysplasia
more frequent surveillance, optimise PPI dose, endoscopic mucosal resection (EMR), radiofrequency albation (HALO), argon
what is gastroparesis
delayed gastric emptying, no physical obstruction
what is symptoms of gastroparesis
feeling of fullness, nausea, vomiting, weight loss, upper abdominal pain
what is the causes of gastroparesis
idiopathic, diabetes mellitus, cannabis, mediation (opiates, anticholinergics), systemic diseases eg systemic sclerosis
what is investigation in gastroparesis
gastric emptying studies
what is the management of gastroparesis
removal of precipitating factors eg drugs liquid/sloppy diet eat little and often promotility agents gastric pacemaker
characteristics of autoimmune chronic gastritis (rarest)
anti-parietal and anti-intrinsic factor antibodies atrophy and intestinal metaplasia in body of stomach
what is consequence of autoimmune chronic gastritic
pernicious anaemia, macrocytic, due to B12 deficiency increased risk of malignancy SACDC
what is H.pylori associated chronic gastritis (most common)
bacteria (gram -ve curvillinear rod) inhabits niche between epithelial cell surface and mucous barrier
what is consequence of H.pylori gastritis
lamina propia plasma cells produce anti H.pylori antibodiesincreased risk of duodenal ulcer, gastric ulcer, gastric carcinoma, gastric lymphoma
what is chemical gastritis
gue to NSAIDs, alcohol, bile refluc direct injury to mucus layer by fat solvents marked epithelial regeneration, hyperplasia, congestion and little inflammation
what is consequence of chemical gastritis
erosions or ulcers
what is peptic ulceration
breach in GI mucosa as result of acid and pepsin attack
what is chronic peptic ulcers
ulcer longstanding and often deep
what are sites predisposed to developing chronic peptic ulcers
1st part of duodenumstomach (junction of body and antrum)oseophago-gastric junctionstomal ulcers
what causes chronic peptic ulcers
not just due to increased acid productionfailure of mucosal defence also important
what is the microscopic view of peptic ulcers
layered appearance, floor of necrotic fibrinopurulent debris, base of inflamed granulation tissue, deepest layer is fibrotic scar tissue
what is complication of peptic ulcers
perforation penetration haemorrhage stenosisintractable pain
what are benign gastric tumours
hyperplastic polypscystic fundic gland polyps
what are malignant gastric tumors
carcinomaslymphomas gastrointestinal stromal tumours
pathogenesis of H.pylori causing gastric adenocarcinoma
H.pylori - chronic gastritis - intestinal metaplasia/atrophy - dysplasia - carcinoma
what are other causes of gastric adenocarcinoma
pernicious anaemia, partial gastrectomy, HNPCC/lynch syndrome, menetriers disease
what is a benign peptic ulcer
mimics cancer but is more punched out and lacks raised rolled edge
where does gastric adenocarcinoma spread
local (other organs and into peritoneal cavity and ovaries - kruckenberg)lymph nodes haematogenous (to liver)
what is a gastric lymphoma (maltoma)
derived from mucosa associated lymphoid tissue (MALT)associated with h.pylori infection continuous inflammation induces evolution into clonal B cell proliferation - if unchecked evolves into high grade B cell lymphoma
what does nausea usually involve
pallor, sweating, excessive salivation and relaxation of stomach and lower oesophagusupper intestinal contractions, forcing intestinal contents by reverse peristalsis into stomach
what is retching
rhythmic reverse peristalsis of stomach and oesophagus forceful contraction of abdominal muscle and diaphragm
what is the events in vomiting
suspension of intestinal slow wave activity retrograde contractions from ileum to stomach suspension of breathing (prevents aspiration)relaxation of LOS - contraction of diaphragm and abdominal muscles compresses stomachejection of gastric contents through open UOS
what cells in mucosa are stimulates by toxic material in gut lumen or systemic toxins
enterochromaffin cells (release mediators eg 5-HT)
what does this stimulation of enterochromaffin cells cause
depolarisation of sensory afferent terminals in mucosa (eg via 5-HT3 receptors)
what does this depolarisation result in
action potential discharge in vagal afferents to brainstem (CTZ - chemoreceptor trigger zone in area postrema - and NTS - nucleus tractus solitarius)
what does this action potential discharge result in
co-ordination of vomiting by vomiting centre
what are consequences of severe vomiting
dehydrationloss of gastric protons and chloride (causes alkalosis)hypokalaemia (mediated by kidney)rarely acidosis may also occur due to loss of duodenal bicarbonateoesophageal damage
what classes of drugs predictably cause nausea and vomiting
cancer chemotherapy (cisplatin, doxorubicin) and radiotherapy general anaesthetic agents with dopamine agonist properties (levodopa in parkinsons)morphine and other opiate analgesicscardiac glycosides (digoxin)drugs enhancing 5HT (SSRIs in depression)
when are 5-HT3 receptor antagonists (setrons eg ondanserton and palonosetron)
used to suppress chemo and radiation induced emesis and post up nausea corticosteroid and NK1 receptor antagonist used in later phase
what kind of vomiting are these drugs not useful for
motion sickness or vomiting induced by agents increasing dopaminergic transmission
what are side effects of 5-HT3 receptor antagonists
constipation and headaches
what drugs can be used for motion sickness
muscarinic acetylcholine receptor antagonists (hyosine, scopolamine)direct inhibition of GI movements and relaxation of GI tract
what is adverse effects of muscarinic acetylcholine receptor antagonists
blurred vision, urinary retention, dry mouth and sedation due to blockage of parasympathetic NS
what is role of histamine H1 receptor antagonists eg cyclizine, cinnarizine and others
motion sickness and acute labyrinthitis and nausea/vomiting caused by irritants in stomach less effective against substances that act on CTZ
what is adverse effects of H1 receptor antagonists
CNS depression and sedation - drowsiness may affect performance of skilled tasks
what is role of dopamine receptor antagonists (domperidone and metoclopramide)
used for drug induced vomiting (chemo, treatment of parkinsons) and vomiting in GI disorders - no motion sicknessblock D2 and D3 receptor in CTZexert prokinetic action on oesophagus, stomach and intestine
why is domperidone superior to metoclopramide
domperidone does not cross BBB and is less likely to result in the many unwanted effects (disorders of movement)
when are NK1 receptor antagonists used
in combo with 5HT in acute phase of highly ementogenic chemo in combination with dexamethasone in delayed phae
when are cannabinoid (CB1) receptor agonists used
in chemo, when not respond to anything else
what is dyspepsia
epigastric pain or burning, postprandial fullness, early satiety
what makes dyspepsia more common
if H.pylori infected or NSAID use overlap with IBS/GORD
what are organic causes of dyspepsia (25%)
peptic ulcer disease, drugs (NSAIDs, COX2 inhibitors), gastric cancer
what are functional causes of dyspepsia (75%)
idiopathic - no evidence of culprit structural disease associated with other functional gut disorders eg IBS
symptoms of uncomplicated dyspepsia
epigastric tenderness
symptoms of complicated dyspepsia
cachexia, mass, evidence gastric outfly obstruction, peritonism
what are the alarm symptoms of dyspepsia
dysphagia, evidence of GI blood loss, persistent vomiting, unexplained weight loss, upper abdominal mass
what is the management of dyspepsia
H.pylori status - eradicate if infected if HP -ve - treat with acid inhibition as required
what kind of pain felt in peptic ulcer disease
epigastric pain - often radiates to backaggravated (duodenum) or relieved (gastric) by eating
what are causes of peptic ulcer disease
H pylori NSAIDs (COX1, COX2, PGE)
characteristics of H.pylori
acquired in infancy, gram -ve in microareophilic flagellated bacillus, oral-oral or faecal-oral spreadconsequences of infection do not arise until later in life
what are consequences of peptic ulcer disease
peptic ulcer diseasegastric cancer (almost all non-cardia gastric adenocarcinoma, also low grade B cell gastric lymphomas)
what is pathophysiology of duodenal ulcer
increased duodenal acid load (metaplasia and H.pylori colonisation), increased acid secretion and thus increased gastrin release (due to decreased somatostatin)
how is H.pylori infection diagnosed
gastric biopsy - urease test, histology and culture/sensitivity urease breath test FAT (faecal antigen test)serology (IgA - not accurate with increased patient age)
what is the treatment of peptic ulcer disease
all antisecretory therapy (PPI)all tested for H pylori (if +ve, eradicate and confirm, if -ve antisecretory therapy)withdraw NSAIDslifestyle
what triple therapy is used alongside PPI for one week
PPI + amoxycillin + clarithromycin PPI + metrondiazole + clarithromycin
what are complications of peptic ulcer disease
anaemia bleedingperforation gastric outlet / duodenal obstruction - fibrotic scar
follow up of duodenal ulcer
uncomplicated DU requires no follow up, only if ongoing symptoms
follow up of gastric ulcer
follow up endoscopy at 6-8 weeks to ensure healing and no malignancy
how does GI bleeding present
haematemesis (vomiting blood)melaena (black bloody faeces)
how to manage GI bleeding
Airway Breathing Circulation airway protection, O2, IV access and fluids
how to assess severity of haemorrhage - rockall risk scoring
Rockall Risk scoring:systolic BP<100mmHgpuse >100Hb<100age>60 comorbid disease postural drop in BPBlatchford Scoring is newer
treatment of bleeding peptic ulcers
endoscopic treatment (high risk ulcer)acid suppression surgery (H.pylori eradication is secondary prevention)
describe the endoscopic treatment of bleeding peptic ulcers (achievement of homeostasis)
injection heater probe coagulationcombinationclipshaemospray (forms mechanical barrier over bleeding site)
which complications cause acute variceal bleeding
sepsis and liver failure
what is the risk factors for acute variceal bleeding
portal pressure >12 mmhgvarices > 25% oesophgageal lumen presence of red signsdegree of liver failure
when would you expect varices in a bleeder
chronic alcohol excess chronic viral hepatitis infection metabolic or autoimmune liver disease intra-abdominal sepsis/surgery on examination - stigmata of chronic liver disease
what is the aims of manageent of variceal bleeding
resuscitationhaemostasisisprevent complications of bleeding prevent deterioration of liver function prevent early re-bleeding
what is the initial considerations in varicel bleeding
coagulopathy (FFP, platelets, vit K)CVP monitoring parenteral vitaminsantibioticshypoglycaemia replace K+, MG2+ and PO42-delirium tremens (perhaps later)
how is haemostasis achieved
1) terlipressin (vasopressin analogue - splanchnic vasoconstrictor)2) endoscopic variceal ligation (banding)3) sclerotherapy 4) sengstaken-blakemore balloon 5) TIPS
