Upper gi pathology

• Metaplasia = Reversible change in which one mature cell

  type is replaced by another cell type = Adaptive response to stress. Can be physiological (cervix). Increased risk of malignancy and considered

  premalignant
• metaplasia eg lung (glandular to squamous), cervix (glandular to squamous), oesophagus (squamous to glandular), muscle (bone formation post injury)
• reflux oesophagitis: pathogenesis [lower oesophageal sphincter tone or inc. abdo pressure = backflow of gastric acid + pepsin] caused by tobacco, alcohol, obesity, pregnancy, medications, hiatus hernia, unknown. clinically synonymous with gastro-oesophageal reflux disease (GERD/GORD)
• endoscopy can be used for diagnosis
• GORD presents as mostly lifestyle interference inc. sleep issues due to heartburn, bleeding, esp. when ulcerated (haematemesis, melaena), dysphagia secondary to stricture (repetitive episodes of damage, inflammation and healing --> circumferential scarring of oesophageal wall --> luminal narrowing), Barrett's oesophagus --> inc risk of adenocarcinoma, superimposed intestinal metaplasia
• Barrett's oesophagus in up to 10% with symptomatic GORD. Increased risk of adenocarcinoma (though <0.5% p.a.). Adaptive response to continued exposure to gastric acid. Turns into type of epithelium that can protect against acid ie small intestine like
• oesophageal cancer is commonest in adult men, insidious onset of symptoms = late discovery, poor prognosis. Either adenocarcinoma (caucasians, reflux oesophagitis & barrets, westen countries) or SCC (alcohol, tobacco, other factors??, african-americans --> more common worldwide)
• SCC --> malignant cells emulating the normal squamous lining of oesophagus
• Cirrhosis → high blood flow resistance through scarred liver → portal hypertension → backpressure opens up the collateral connections between the portal and systemic circulations to bypass liver (shunting). causes haemorrhoids, caput medusae, oesophageal varices (fragile dilated collateral veins in oesophageal submucosa --> can bleed catastrophically
• Mallory-Weiss tear = mucosal tear from failure of normal relaxation of gastro-oesophageal musculature during vomition --> usually heals rapidly and completely without treatment. This is haematemesis
• eosinophilic oesophagitis --> caused by t cells abnormally recruiting eosinophils to sites of injury. usually children and young adults, mid oesophagus. M >>F. presents with nausea, vomiting, dysphagia and chest pain
• Stomach has

  Two main types of mucosal lining. Acid secreting (Body and fundus)

  Non acid secreting (Cardia and antrum/pylorus)
• mucin barrier is more prevalent in the antrum to protect the mucosa surface from the chyme
• gastritis = stomach inflammation. can be active (acute) or chronic (often a mixture). Many causes but h. pylori a chief culprit (over 50% world pop. infected)
• acute gastritis = surface epithelial degeneration, regenerative hyperplasia of pit-lining epithelium, vasodilation/congestion, neutrophil polymorph response
• chronic gastritis = lymphocyte and plasma cell response, glandular atrophy, lamina propria fibrosis, metaplasia
• acute/chronic gastritis = helicobacter pylori infection, bile reflux, iron tablets, immunotherapy cancer drugs. chronic can also be caused by autoimmune issues
• Active (acute) = vascular congestion, oedema, neutrophils in GIT (ABNORMAL)
• chronic gastritis = chronic inflammatory cells in the lamina propria. plasma cells, lymphocytes, some eosinophils (can be independent of parasites). Architecture changes --> glands look funny (reactive), loss of mucin in cells

  
• clues that h. pylori is the problem: active component (neutrophils), lymphoid cells forming aggregates, plasma cells usually dense (ie sever chronic inflammation)
• h. pylori uses urease enzyme to convert the urea in the stomach into ammonia and carbon dioxide to protect itself by neutralising gastric acid. produces toxins that damage surrounding tissue, don't produce mucin, direct damage = ulcers
• h. pylori induced gastritis = colonisation of gastric mucosa, lifelong without treatment, chronic +/- active component
• Marshall and Warren discovered h. pylori in 1980s and showed relation to peptic ulcers. prior, thought to be caused by stress --> hypersecretion of gastric acid and pepsin
• h. pylori confirmed by presence on mucosal surface in gastric biopsy. urea breath test. on spot result. ammonia production by h. pylori urease can be detected. treatment can begin while waiting for biopsy confirmation
• giemsa stains highlight h pylori
• h. pylori --> complications = peptic ulcer (epigastric pain [post-prandial, night, relieved by alkali and food], iron deficiency anaemia, haemorrhage, perforation, nausea, vomiting, weight loss). atrophic gastritis (every wanes), lymphoma (MucosaAssociatedLymphomaTissue, treatment can cause remission), gastric cancer (intestinal metaplasia like in barret's oesophagus)
• h. pylori is gram-negative bacterium that infects the stomach. most frequently the antrum. dyspepsia, epigastric pain, nausea, vomiting, GI bleeds (can be asymptomatic). treatment is antibiotics + PPIs
• peptic ulcer = ulceration in parts of the GIT bathed by gastric juice. mostly in stomach (body, antrum) or duodenal bulb (1st part). 2nd part neutralises luminal pH through alkaline secretions from pancreas and biliary tree
• peptic ulcers can occur in oesophagus 2ndary to GORD, mainly erosions rather than frank ulers. Jejunum; gastro-jejunal surgical anastomosis, unless acid secretion is blocked
• ulcer = break in the epithelium. No mucosa/epithelium, just lined with granulation tissue. Ulceration is defined as a break through full thickness of mucosa into at least the submucosa. Erosion is confined within mucosa.
• peptic ulcers can be caused by h pylori or NSAIDs
• NSAIDs block prostoglandin synthesis
• ~10% in older studies of gastric ulcers are actually carcinomas, but duodenal ulcers are almost always benign
• atrophic gastritis = loss of parietal cells in acid-secreting parts of stomach (mainly body). no acid or intrinsic factor. Chronic gastritis → diffuse destruction of body glands (loss of parietal cells) → loss of intrinsic factor → inability to absorb vitamin B12 from terminal ileum → megaloblastic/pernicious anaemia. either h. pylori or autoimmune destruction of parietal cells.
• low acid causes hyperplasia to compensate, but body physically can't, can cause tumours
• Chronic (atrophic) gastritis often leads to intestinal metaplasia and adenocarcinoma. pre malignant = increased surveillance needed.
• gastric cancer frequently metastasizes to the liver and rest of peritoneal cavity. chronic h. pylori infection increases risk.
• two types of gastric cancer (both adenocarcinomas): Intestinal [malignant glands, well defined mass, more common in Japan, South America, Eastern Europe, M>F]. Diffuse (poorly differentiated vs signet ring cell) [sheets of malignant cells arranged singly, linitis plastica (diffuse thickening of the gastric wall), similar incidence across countries, M=F]
• gastric adenocarcinoma - intestinal type - resembles peptic ulcer macroscopically. microscopically, malignant glands with irregular, complex architecture lined by cells with dark, irregular nuclei
• Gastric adenocarcinoma - diffuse type - diffuse thickening and hardening of gastric wall. microscopically, invasion by individual tumour cells with associated fibrotic stromal reaction