pathology of the oral and digestive system: upper GI

week 7 human path

GI system

• upper GI

• lower GI

• accessory organs

upper GI

• oral cavity

• pharynx

• oesophagus

• stomach

• duodenum

lower GI

• Jejunum
• Ileum
• Caecum
• Ascending colon
• Transverse colon
• Descending colon
• Sigmoid colon
• Rectum
• Anus
• Accessory Organs
• Liver
• Pancreas
• Gall bladder

accessory organs

• liver

• pancreas

• gall bladder

histology

4 main layers of wall:

• mucosa

• submucosa

• muscle

• serosa/adventitia

-nerve plexus

-blood and lymph vessels

-specialisms related to region

functions of digestive system

• Breakdown of proteins, fats, carbohydrates to constituents
for absorption
• Absorption of breakdown products and vitamins, and
minerals.
• Mechanical digestion
• Teeth to “small lumps”
• Stomach to chyme
• Chemical digestion
• Enzymes mouth (saliva), stomach and mainly SI
• Absorption
• Small intestine all nutrients
• Large intestine mainly water
Main functions of the GI system

pathology of oral cavity

• inflammatory lesions

  • aphthous ulcers: unknown aetiology

  • herpes simplex infection (cold sores)

  • other viruses: coxsackie, herpes zoster,

  • candidiasis (thrush)

• proliferative lesions

  • fibromas

  • intra-oral legions that become malignant: leukoplakia, erythroplakia, lichen planus

  • squamous cell carcinoma

    • HPV +ve : caused by human papilloma
      (especially HPV16)

    • HPV -ve : often caused by alcohol and
      tobacco, areca nut
      
      

  
  

pathology of salivary glands

• ptyalism (excessive saliva)

• xerostomia (dry mouth, variety of causes: drugs, dehydration)

• sialadenitis (inflammation of gland)

  • mumps virus

  • bacteria: staph cocc

  • autoimmune obstruction

• salivary duct obstruction

  • calculus (kidney stones)

  • painful swelling of submandibular gland

• neoplasms

  • most parotid gland

  • pleomorphic adenoma

    • slow growing tumour

    • 15% become malignant

  • mucoepidermoid carcinoma

    • carcinoma composed of mucous cells and epithelial cells

esophageal pathology

Function: rapid transit from mouth to
stomach
• Symptoms: dysphagia, “heartburn”,
acid regurgitation, painful swallowing
• Obstruction: stricture, tumour
• GORD/GERD
• Hiatus Hernia
• Cancer

• squamous cell- upper oesophagus

• adenoma: lower oesophagus
  

hiatal hernia and esophagitis

• hernia: small part of stomach slips through diaphragm into middle compartment of chest

• can give GERD

• oesophagitis

  • inflammation often due to reflux

GERD (gastroesophageal reflux disease)

• acid moves from stomach to oesophagus

• causes: weak sphincter, pregnancy, obesity, large meals, smoking

esophageal cancer

adenocarcinoma:

• cancer of glandular cells

• most common esophageal cancer

• often result of chronic gastric reflux

• lower third of esophagus

• UK, Europe, USA

squamous cell carcinoma

• cancer of epithelial cells

• associated with poverty, alcohol and tobacco

• middle and upper third of esophagus

• China, Africa

stomach

• mechanical function: churning to reduce size to chyme

• chemical function: acid, pepsin

gastric pathologies

• anatomic disorders: pyloric stenosis

  • congenital abnormality

  • thickening of sphincter, hypertrophy of pylorus muscle

  • result narrowing, impedes gastric emptying

• inflammatory disorders: gastritis

  • acute inflammatory character

  • more commonly chronic

• ulcerative disorders: peptic and acute gastric

  • acute: submucosa from unsult

  • chronic: increased acid, ischaemia, reduction in defences

• neoplastic disorders

  • adenocarcinomas either intestinal or diffuse dependent on cell of origin

• hypertrophic gastropathies

  • menetrier disease, zollinger-ellison syndrome

menetrier disease

• unknown aetiology

• enlargement of gastric rugae

  • hyperplasia and hypersecretion

• expansion and hypersecretion of surface epithelial cell

  • loss of protein

  • hyperalbuminaemia

  • peripheral oedema

gastric ulcers

• break in lining of stomach

• can involve multiple layers

• 0.5cm or larger

• causes include:

  • H.pylori, major cause

  • NSAIDs and aspirin by 4x

  • stress

  • ischaemia, drugs, metabolic disturbances, cytomegalovirus, radiotherapy, crohn’s diseases, vasculitis

symptoms of gastric ulcers/chronic gastritis

• abdominal (epigastric) pain

  • associated with eating

• bloating and abdominal fulness

• nausea and copious vomiting

• loss of appetite and weight loss

• haematemesis (vomiting up blood)

• melaena

  • tarry, foul smelling faces

  • presence of oxidised iron from Hb

  • perforated ulcer

    • requires immediate surgery

Helicobacter pylori

• gram-ve, spiral shaped

• survives in acid

  • microaerophilic due to hydrogenase enzyme

• common cause of chronic infection

• most never get symptoms

• but can cause ulcers

virulence factors that enable H pylori to survive in human host

• flagella gives motility and enables bacteria to grow under mucosal membrane

• lipopolysaccharides and membrane proteins adhere to host cell receptors

• urease enzyme is used to combat acidic environment of stomach by producing ammonia

  • gives test for its presence

schematic diagram of H pylori infection and pathogenesis

• urease neutralises acid

• moves to epithelium using flagella

• bacterial adhesins interact with host cell receptors

• gives colonisation and infection

• release of proteins and toxins

• result: damage

how H pylori damages intestinal mucosa

• Vac A causes:

  • alterations in mitochondrial membrane permeability and apoptosis

  • stimulation of pro-inflammatory signalling

  • increased permeability of plasma membrane

  • alterations in endocytic compartments

  • in lamina propria interferes with activation and proliferation of T lymphocytes

proportions of individuals with differing disease severity

• causes gastritis

• increasing degenerative changes to atrophy

• increased risk of developing precancerous lesions

• association with gastric cancer

• strong association with poor socioeconomic conditions

gastric disease diagnosis

• antibody blood test

  • not necessarily present

• breath test: 14C labelled urea drink, detection of isotope in exhaled CO2 will indicate presence of urease secreted by H pylori

• biopsy taken during endoscopy, tissue sample examined in lab for presence of H pylori

• x-ray examination after barium meal

treatment and prevention

• triple therapy with clarithromycin, amoxicillin and proton pump inhibitors

• antibiotic resistant strain an increasing risk

• partial gastrectomy as an extreme option

• vaccine in development (only single vaccine so far_

H. pylori and cancer

• major risk factor:

  • change in mucosa to non atrophic gastritis to precancerous lesion to atrophic gastritis and intestinal metaplasia

• mechanisms

  • cagA and peptidoglycan trigger oncogenic pathways

  • inflammation induced by H pylori involves cyclooxygenase

  • 2/prostaglandin E2 pathway and IL 1beta → chronic active gastritis and adenocarcinoma

  • oxidative stress and dysregulated E-cadherin/beta catenin/p120 interactions

types of gastric cancers

• gastric polyps

  • 10% are adenomas which develop into adenocarcinomas

• adenocarcinomas

  • most common gastric cancer (90%)

  • incidence very high in japan and chile

  • 10% associated with EPV

• lymphomas

  • stomach is most common location (5%0 of stomach cancers

  • in GI they’re called MALT (mucosa associated lymphoid tissue)

• carcinoid tumouts

  • slow growing neuroendocrine tumours

• gastrointestinal stromal tumours

  • non epithelial cells

NSAIDs and gastric ulcers

• peptic ulcers as complication of NSAID use

• inhibition of COX-1

• reduced PG secretion

• loss of PG cytoprotection

• increases susceptibility to mucosal injury

GPS (gastroprotective strategy)

• prostaglandin analogues

  • PGE1, analogue misoprostol

• cyclooxygenase 2 inhibitors

  • celecoxib, 50% GI complications of COX-1 inhibitors, CV risk

• proton pump inhibitors

  • omeprazole