Gastrointestinal and Liver Flashcards
GIT Arrangement (Layers)
- Mucosa (ELMM) 2. Submuscosa 3. Muscularis externa 4. Adventitia/serosa
Oesophagus
Muscular Tube Sphincters at top and bottom - Close between swallows - Prevent entry of gastric acid - Impairment can corrode oesphagus
Stomach
- Storage
- Digestion: mixing
- First fine of defence against infectious agents
Duodenum
First part of small intestine Receives: - Partially digested chyme from stomach - Bile from liver - Pancreatic juices
Stomach Secretions
2.5 - 3L per day
Pepsinogens: produced by chief cells
Acid (HCl): produced by parietal cells
Intrinsic factor: Produced by parietal cells - required for absorption of Vit D
Stomach/Duodenum Defences Against Acid
- Mucus production
- Bicarbonate production
- Prostaglandin production
- Tight junctions
- Rapid gastric epithelial regeneration
Peptic Ulcers
Breach in the mucosa of the stomach or duodenum (usually distal stomach or proximal duodenum) that is produced by the action of gastric secretions
- Imbalance between gastroduodenal mucosal defence mechanisms and the damaging agents (acid and pepsin)
- Gastric acid and pepsin are prerequisites
- Acute and chronic inflammation
Layers of Peptic Ulcer
- Necrotic slough
- Acute inflammatory exudate
- Vascular and fibrovascular granulation tissue
- Fibrous scar
- Heal from bottom to the top (opposite to usual healing)
H Pylori: why can survive in stomach
- Small gram neg rods with flagella
Can survive in stomach because: - Able to bore into protective mucus layer (cork screw motion)
- Motile (swim through viscous mucus)
- Produces substances that buffers gastric acid
- Can adhere to gastric epithelial cells (prevent being washed away by constant contractions of stomach)
Action of H. Pylori
- Enhances gastric acid secretion and impairs production of bicarbonate buffer -> reduction in pH
- Secretes substances which damage surface epithelial cells and weaken the junction between cells
- Promotes an inflammatory response, recruits inflammatory cells that release mediators -> collateral damage
Chronic use of NSAIDs
- Damages mucus layer of GIT (decreased prostaglandins -> decreased bicarbonate, mucus, blood flow)
- Allows acid/pepsin to come into contact with mucosa
Symptoms of Chronic Peptic Ulcers
Epigastric pain Burning Anaemia Vomiting Nausea Bloating Weight loss
Treatment of Peptic Ulcers
Eradicate the cause: treat H.pylori infections, discontinue NSAIDs and reduce acid secretion
Outcomes of Peptic Ulcers
- Healing: overcome damaging stimulus and defect fills with fibrous scar
- Bleeding: penetrate into blood vessels
- Perforation: gastric acid -> extensive damage and ulcer extends transmurally -> can lead to pancreatitis or peritonitis -> septicaemia
- Obstruction: scarring can lead eventually lead to constriction, especially in pylorus
GERD
Failure of lower oesophageal sphincter
If other defence mechanisms of oesophagus (gravity, swallowing, saliva) are overwhelmed -> mucosal damage
GERD Pathogenesis
Oesophageal mucosal damage from either:
- decreased salivation
- impaired oesophageal clearance
- decreased LES resting tone
- delayed gastric emptying
GERD Complications
Mucosal damage -> oesophagitis
- If persists -> erosion of luminal surface - ulceration
Oesophageal strictures (abnormal narrowing or tightening)
- Due to fibrosis and healing
Barrett’s Oesophagus: normal squamous epithelium is replaced by columnar epithelium -> associated with increased risk of oesophageal cancer
Small Intestine Function
- Digestion
- Nutrient and water absorption
Large Intestine Function
- Mainly water absorption
- Absorption of remaining nutrients and vitamins
- Compacts bolus and stores fecal matter in rectum
Inflammatory Bowel Disease
- Main types: Crohn’s and Ulcerative Colitis
- Chronic but relapsing diseases
- Aetiology: combination of genetic, environmental and immunological factors
- Onset usually in young adults
IBD: Pathogenesis
Defective host interactions with intestinal microfloral
->
Epithelial dysfunction
->
Aberrant mucosal inflammatory responses (chronic inflam)
- Persistent activation of the immune system
- Destructive local immune response (T cell activation)
IBD: extra-intestinal complications
Mainly related to malnutritions and ongoing joint inflammation
- Join pain (arthritis)
- Skin conditions
- Eye inflam
- Liver disorders
- Osteoporosis
Crohn’s Disease
- Affects any part of the GIT (Mainly SI)
- Usually diagnosed 15-30 yrs old
- Can be familial
- 2-4 times more common in smokers
- F > M
- TNF-alpha thought to be a major factor
Crohn’s Disease: Symptoms
- Intermittent attacks
- Weight loss
- Perianal fissures
- Malabsorption -> malnutrition
- Aching joints, skin rashes, eye inflam
Crohn’s Pathology” Macroscopic
- Transmural inflammation - granulomatous (non-caseating necrosis)
- Skip lesions - mucosal ulcers
- Bowl and adjacent mesentery: thickened and oedematous, mesenteric lymph nodes enlarged, firm and mattered together
- Creeping fat: extension of mesenteric fat
- Cobblestone appearance: nodular swelling and fibrosis, focal mucosal ulcers
Crohn’s Disease: Complications
- Bowel obstruction
- Ulcers
- Malabsorption of specific nutrients/vitamins if involves small bowel
- Fistulas to other organs, including bladder and vagina, peri-anal (common) -> septicaemia
- Anaemia
Crohn’s Disease: Treatment
- No cure
- Medications: corticosteroids
- Surgical resection
- Drainage of abscesses
Ulcerative Colitis
- LARGE INTESTINE only
- Chronic inflam disease of the colon
- Affects rectum and extends proximally
- Predominantly mucosa involvement (superficial ulceration!)
- Diagnosis 15-30 and 50-70 years
Colon - ALWAYS involved
Rectum - usually involved
Anus - seldom involved
UC: Symptoms
- Abdominal pain
- Blood or pus in stool
- Diarrhoea
- Proctitis (inflammation of rectum)
- GI bleeding
UC: Macroscopic
- Superficial erosions or ulcers
- Mucosal surface = red, raw and granular
- Mucosal folds are lost (atrophy)
- Inflammatory polpys
UC: Treatments
- Diet
- Mild/moderation: anti-inflammatories or immunosuppressive drugs
- Severe: surgical resection of inflamed/dysfunction region
Coeliac Disease
- Autoimmune disease
- Genetic predisposition
- Hypersensitivity reaction to gluten
- Triggers immune system to damage mucosa
- Generalised malabsorption
- SI mucosal lesions
CRC: Risk Factors
- Age
- Prior CRC
- IBD
- Lifestyle: smoking, alcohol, obesity
- Genetic factors
- Diet: fibre, fat, meat
Polyps
- BENIGN
- Lesion that protrudes into the lumen
- Non neoplastic or neoplastic
Adenomatous Polyps
- Neoplastic
- Direct precursor of adenocarcinoma
- Can be pedunculated or sessile (flat)
- Generally asymptomatic
- Adenomas divided into 3 subtypes based on histology: tubular, tubulovillous or villous
Familial Adenomatous Polyposis (FAP)
- An inherited disorder characterised by 100-1000s of adenomas along mucosa (genetic defect is mutation of APC gene on Chr 5)
- Polyps develop by late teens
- CRC occurs in all patients if untreated
- Total colectomy (removal of entire colon) before onset of cancer is curative
CRC: Pathology
- Polypoid, ulcerating, infiltrative, annular (ring shaped) and constrictive
- Majority are adenocarcinomas
- Commonly metastasis to lived
CRC: Clinical Features
- Can be asymptomatic for years
- Most common clinical sign: occult faecal blood
- Left CRC: smaller lumen and solid faeces, produces obstructive symptoms, change in bowel habits, abdominal pain
- Right CRC: wider lumen and liquid faeces, chronic asymptomatic bleeding, anaemia
