GI PATHOLOGY Flashcards by arcie cola

Normal anatomy and function
• Hollow tube extending from ______ to ______, with regional variations in structure and function

oral cavity, anus

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Normal anatomy and function
• Important functions: ______, ______, ______, ______ and ______

Motility, secretion, digestion, absorption, excretion

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Manifestations of GI diseases

GI diseases may be:

(i) Limited to GIT e.g. peptic ulcer
(ii) Manifestation of systemic disorder e.g. CMV infection
(iii) Presents as a systemic disorder but resulting from GI problem e.g. Iron deficiency anaemia from bleeding PUD, vitamin deficiencies due to malabsorption

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Manifestations of GI diseases

Cardinal signs and symptoms:

Abdominal / chest pain, altered ingestion of food (nausea, vomiting, dysphagia, anorexia), altered bowel movements (diarrhoea or constipation), GI bleeding

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Manifestations of GI diseases

Complications: Acute – ______, ______, ______, ______

dehydration, sepsis, bleeding, perforation

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Manifestations of GI diseases

Complications: Chronic: ______ (malnutrition, deficiency states), ______

Malabsorption, obstruction

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Congenital anomalies:

• Atresia, fistulae and duplications
• Diaphragmatic hernia, omphalocele and gastroschisis
• Ectopia
• Meckel diverticulum
• Pyloric stenosis
• Hirschsprung disease (congenital aganglionic megacolon)

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Congenital anomalies

______
• May occur in any part of the GIT

Atresia, fistulae and duplications

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Congenital anomalies

Atresia, fistulae and duplications
• ______ = absence

Agenesis

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Congenital anomalies

Atresia, fistulae and duplications
• ______ = incomplete development (often resulting in a thin non-canalised cord)

atresia

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Congenital anomalies

Atresia, fistulae and duplications
• ______ = developmental or acquired luminal narrowing due to thickening of the wall. Causes complete / partial mechanical obstruction requiring surgical repair

stenosis

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Congenital anomalies

Atresia, fistulae and duplications

______: may be associated with a fistula connecting the oesophagus to the tracheobronchial tree (tracheo-oesophageal fistula); fistula may also be present without atresia. Results in aspiration, pneumonia, fluid and electrolyte imbalances

esophageal atresia

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Congenital anomalies

Atresia, fistulae and duplications

______: frequently duodenal, or imperforate anus (most common)

Intestinal atresia

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Congenital anomalies

Diaphragmatic hernia, omphalocele and gastroschisis

______
• when incomplete formation of the diaphragm allows herniation of the abdominal viscera into the thoracic cavity. If severe, may result in pulmonary hypoplasia

Diaphragmatic hernia

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Congenital anomalies

Diaphragmatic hernia, omphalocele and gastroschisis

Diaphragmatic hernia

______
• Due to separation of diaphragmatic crura and widening of space between muscular crura and esophageal wall. Can be congenital or acquired.

Hiatus hernia

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Congenital anomalies

Diaphragmatic hernia, omphalocele and gastroschisis

Diaphragmatic hernia

______
• Associated with reflux oesophagitis and may be a cause of lower oesophageal sphincter incompetence; may be complicated by ______, ______, ______, ______ (______), increased risk of ______ and ______

Hiatus hernia, ulceration, bleeding, perforation, strangulation, paraoesophageal hernia, esophageal, gastric adenocarcinoma

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Congenital anomalies

Diaphragmatic hernia, omphalocele and gastroschisis

______
• incomplete closure of abdominal musculature, with herniation of the abdominal viscera into a ______. Due to failure of midgut to return to abdomen during midgut rotation. ______% of infants have other associated birth defects (especially heart and renal anomalies)

Omphalocele, ventral membranous sac, 40

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Congenital anomalies

Diaphragmatic hernia, omphalocele and gastroschisis

______
• similar to omphalocele except it involves all layers of the abdominal wall from peritoneum to skin and therefore has ______. Due to defective ingrowth of mesoderm, impaired midline fusion or inappropriate apoptosis. ______-______% may have associated intestinal atresia, but associated anomalies are otherwise rare.

Gastroschisis, no covering sac, 10, 15

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Congenital anomalies

______
• normally formed tissues in an abnormal site (‘developmental rests’). Common in GIT e.g. ectopic gastric mucosa in upper oesophagus (‘______’) or small bowel/colon, ectopic pancreatic tissue in oesophagus / stomach. Can cause inflammation and scarring with occult bleeding and/or pain

Ectopia, inlet patch

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Congenital anomalies

Meckel diverticulum:

• True diverticulum
• Acquired diverticulum

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Congenital anomalies

Meckel diverticulum

______
• blind outpouching of the GIT that communicates with the lumen and includes all three layers of the bowel wall

True diverticulum

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Congenital anomalies

Meckel diverticulum

______
• lacks or has an attenuated muscularis propria e.g. in ______

Acquired diverticulum, sigmoid colon

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Congenital anomalies

______
• is the most common true diverticulum as a result of failed involution of the ______ (connects lumen of developing gut on the antimesenteric side to yolk sac). Often contains ectopic gastric tissue which may result in occult bleeding

Meckel diverticulum, vitelline duct

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Congenital anomalies

Meckel diverticulum

______
• occurs in 2% of population, within ______ (______) of ileocaecal valve, ______ (______) long, twice as common in ______ and most often symptomatic by age ______ (although only ______% are ever symptomatic)

‘Rule of ‘2’s’, 2 feet, 60 cm, 2 inches, 5 cm, males, 2, 4

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GI Congenital anomalies Pyloric stenosis:

• Congenital vs acquired • Congenital hypertrophic pyloric stenosis • Hyperplasia of the pyloric muscularis propria +/- oedema and inflammation

GI Congenital anomalies Pyloric stenosis ______ vs ______ (e.g. ______ / ______, ______)

Congenital, acquired, antral gastritis, peptic ulcers at pylorus, carcinomas of distal stomach or pancreas

GI Congenital anomalies Pyloric stenosis ______ • is 3-5x more common in males and has strong but multifactorial pattern of inheritance and genetic basis

Congenital hypertrophic pyloric stenosis

GI Congenital anomalies Pyloric stenosis ______ • results in gastric outlet obstruction, usually presenting between ______-______th wks of life as projectile non-bilious vomiting after feeding. Surgical splitting of the muscularis (______) is ______

Hyperplasia of the pyloric muscularis propria +/- oedema and inflammation, 3, 6, myotomy, curative

GI Congenital anomalies ______ • 1 in 5000 live births; 10% of all cases occur in ______

Hirschsprung disease (congenital aganglionic megacolon), Down syndrome

GI Congenital anomalies ______ • Absence of neural crest derived ganglion cells (both ______ and ______) in the distal colon due to (1) ______, or (2) ______. This results in absent peristalsis and functional obstruction, with dilatation of the proximal unaffected bowel segment

Hirschsprung disease (congenital aganglionic megacolon), Meissner submucosal, Auerbach myenteric plexus, premature arrest of normal migration of neural crest cells from caecum to rectum, premature death of ganglion cells

GI Congenital anomalies ______ • Presents with failure to pass meconium in the immediate postnatal period, followed by constipation, abdominal distension and bilious vomiting, which may be complicated by enterocolitis, fluid and electrolyte imbalances, perforation and peritonitis. Treatment: ______

Hirschsprung disease (congenital aganglionic megacolon), surgical resection

______ • Extends from epiglottis in pharynx to gastro-oesophageal junction

ESOPHAGUS

ESOPHAGUS Clinical presentations:

Dysphagia, haemetemesis, odynophagia (painful swallowing), heartburn

ESOPHAGUS Non-neoplastic conditions:

congenital anomalies, obstruction, lacerations/perforation, varices, oesophagitis, Barrett oesophagus

ESOPHAGUS Tumours:

most commonly adenocarcinoma and squamous cell carcinoma

ESOPHAGUS:

• Obstruction • Lacerations / perforation • Varices • Esophagitis • Barrett esophagus (BE) • Adenocarcinoma • Squamous cell carcinoma

ESOPHAGUS Obstruction ______ (mechanical) vs ______ (dysmotility i.e. disruption of the coordinated waves of peristaltic contractions following swallowing)

Structural, functional

ESOPHAGUS Obstruction Mechanical obstruction:

stenosis / strictures due to inflammation and scarring (GERD, radiation, caustic injury), mucosal webs or rings, cancer

ESOPHAGUS Obstruction Functional:

• Achalasia

ESOPHAGUS Obstruction Functional ______ • triad of (1) ______, (2) ______ and (3) ______.

Achalasia, incomplete lower oesophageal sphincter (LES) relaxation, increased LES tone, aperistalsis of the oesophagus

ESOPHAGUS Obstruction Functional Achalasia:

• Primary achalasia • Secondary achalasia

ESOPHAGUS Obstruction Functional Achalasia • ______ = due to distal oesophageal inhibitory neuronal (ganglion cell) degeneration. Cause is unknown

Primary achalasia

ESOPHAGUS Obstruction Functional Achalasia • ______ = e.g. ______ where ______ infection causes destruction of the myenteric plexus, failure of peristalsis and oesophageal dilatation; diabetic autonomic neuropathy etc.

Secondary achalasia, Chagas disease, Trypanosoma cruzi

ESOPHAGUS ______ • One of the causes of haemetemesis

Lacerations / perforation

ESOPHAGUS Lacerations / perforation:

• Mallory-Weiss tears • Boerhaave syndrome

ESOPHAGUS Lacerations / perforation ______ • superficial longitudinal tears near the GEJ, most often associated with severe retching due to acute alcohol intoxication. Thought to be due to failure of the reflex oesophageal musculature relaxation preceding the antiperistaltic contractile wave, causing stretching and tearing of the oesophagus by the refluxed gastric contents.

Mallory-Weiss tears

ESOPHAGUS Lacerations / perforation ______ • Does not usually require surgical intervention

Mallory-Weiss tears

ESOPHAGUS Lacerations / perforation ______ • transmural tearing and rupture of the distal oesophagus, also usually associated with vomiting, causing severe mediastinitis.

Boerhaave syndrome

ESOPHAGUS Lacerations / perforation ______ • Requires urgent surgical intervention.

Boerhaave syndrome

ESOPHAGUS ______ • Tortuous dilated veins primarily within submucosa and lamina propria of distal oesophagus and proximal stomach

Varices

ESOPHAGUS ______ • Consequence of portal hypertension, which causes the development of porto-systemic collateral channels. Present in nearly ______% of cirrhotic patients, with variceal rupture and bleeding in ______-______% (manifesting as ______) which is an emergency treated medically or endoscopically. However, ______% or more of patients with variceal haemorrhage still die from hypovolemic shock, hepatic coma etc., and those that survive may have recurrent bleeds with mortality risk. ______ with ______ with ______ to reduce portal blood flow and endoscopic variceal ligation helps mitigate the risk.

Varices, 50, 25, 40, haematemesis +/- melena, 30, Surveillance, prophylactic treatment, beta- blockers

ESOPHAGUS Esophagitis:

• Reflux oesophagitis (gastro-oesophageal reflux disease or GERD) • Eosinophilic oesophagitis • Chemical • Radiation • Infections (immunocompetent vs immunocompromised) • Graft-vs-host disease • Involvement by skin diseases

ESOPHAGUS Esophagitis ______ • Most frequent cause of oesophagitis. Reflux of gastric juices +/- duodenal bile results in ______

Reflux oesophagitis (gastro-oesophageal reflux disease or GERD), oesophageal mucosal injury

ESOPHAGUS Esophagitis Reflux oesophagitis (gastro-oesophageal reflux disease or GERD) Pathogenesis:

(1) Transient LES relaxation (2) Abrupt increase in intra-abdominal pressure

ESOPHAGUS Esophagitis ______ • Pathogenesis ______: mediated by vagal pathways and triggered by gastric distension, stress, swallowing-induced

Reflux oesophagitis (gastro-oesophageal reflux disease or GERD), Transient LES relaxation

ESOPHAGUS Esophagitis ______ • Pathogenesis ______: causes forceful opening of a relatively hypotensive LES e.g. coughing, straining. Stratified squamous epithelium of the oesophagus is resistant to abrasion from foods but sensitive to acid, triggering an inflammatory response.

Reflux oesophagitis (gastro-oesophageal reflux disease or GERD), Abrupt increase in intra-abdominal pressure

ESOPHAGUS Esophagitis ______ • Risk factors: alcohol, smoking, obesity, CNS depressants, pregnancy, hiatal hernia, delayed gastric emptying and increased gastric volume

Reflux oesophagitis (gastro-oesophageal reflux disease or GERD)

ESOPHAGUS Esophagitis ______ • Clinical features: Most common in individuals above 40, but can occur in infants and children. Usually presents with heartburn, dysphagia, sore throat and acid regurgitation. May be complicated by ulceration, haemetemesis, melena, strictures, Barrett oesophagus. Proton-pump inhibitors (PPI) to reduce gastric acidity provides symptomatic relief

Reflux oesophagitis (gastro-oesophageal reflux disease or GERD)

ESOPHAGUS Esophagitis ______ • Histology: basal zone hyperplasia, elongation of the lamina propria papillae, intraepithelial eosinophils and neutrophils

Reflux oesophagitis (gastro-oesophageal reflux disease or GERD)

ESOPHAGUS Esophagitis ______ • most common cause of GERD-like symptoms in children living in developed countries.

Eosinophilic oesophagitis

ESOPHAGUS Esophagitis ______ • Strongly associated with atopy - food allergy, allergic rhinitis, asthma or modest peripheral eosinophilia.

Eosinophilic oesophagitis

ESOPHAGUS Esophagitis ______ • Histology: large numbers of intraepithelial eosinophils

Eosinophilic oesophagitis

ESOPHAGUS Esophagitis Eosinophilic oesophagitis Treatment:

dietary restriction to food allergens and topical / systemic corticosteroids. A subset may respond to PPIs.

ESOPHAGUS Esophagitis Chemical:

irritants e.g. alcohol, corrosive acids/alkalis, pill-induced, chemotherapy

ESOPHAGUS Esophagitis Radiation:

vascular injury resulting in mucosal damage

ESOPHAGUS Esophagitis Infections (immunocompetent vs immunocompromised):

Herpes simplex virus (HSV), cytomegalovirus (CMV), fungal e.g. Candidiasis

ESOPHAGUS Esophagitis Infections (immunocompetent vs immunocompromised) • ______ [punched-out ulcers, epithelial viral nuclear inclusions]

Herpes simplex virus (HSV)

ESOPHAGUS Esophagitis Infections (immunocompetent vs immunocompromised) • ______ [shallower ulcers, stromal nuclear and cytoplasmic inclusions]

cytomegalovirus (CMV)

ESOPHAGUS Esophagitis Infections (immunocompetent vs immunocompromised) • fungal e.g. ______ [adherent gray-white pseudomembranes, fungal hyphae]

Candidiasis

ESOPHAGUS Esophagitis ______ • basal epithelial cell apoptosis without significant acute inflammation

Graft-vs-host disease

ESOPHAGUS Esophagitis Involvement by skin diseases e.g. ______

bullous pemphigoid

ESOPHAGUS ______ • Complication of chronic GERD characterized by columnar / intestinal metaplasia within the oesophageal squamous mucosa.

Barrett esophagus (BE)

ESOPHAGUS ______ • Clinical features: Rising incidence, ~10% of individuals with symptomatic GERD. White males, 40-60yo. Risk factor for dysplasia (preinvasive change) and oesophageal adenocarcinoma. Presence ofdysplasia a/w prolonged symptoms, longer segment length, increased patient age and Caucasian race. Management is controversial, but most currently do periodic endoscopy with biopsy for dysplasia surveillance. Intramucosal or submucosal invasive carcinoma requires treatment.

Barrett esophagus (BE)

ESOPHAGUS ______ • Diagnosis requires endoscopy and histology.

Barrett esophagus (BE)

ESOPHAGUS ______ • Endoscopy: tongues / patches of red velvety mucosa extending upward from the GEJ, alternating with the pale smooth squamous oesophageal mucosa and interfacing distally with the light brown columnar gastric mucosa. Long segment = ______ cm or more, short segment = less than ______ cm

Barrett esophagus (BE), 3, 3

ESOPHAGUS ______ • Histology: columnar / intestinal metaplasia (requirement of goblet cells depends on UK/US guidelines). Dysplasia is characterized by architectural and cytologic atypia, and can be low or high grade.

Barrett esophagus (BE)

ESOPHAGUS ______ • Most oesophageal adenocarcinomas arise from ______ usu. distal 1/3 of oesophagus, may involve the gastric cardia

Adenocarcinoma, Barrett oesophagus

ESOPHAGUS ______ • Risk factors: GERD, smoking, radiation, reduced rates of H.pylori infection (because H.pylori causes gastric atrophy which reduces acid secretion and reflux and therefore Barrett oesophagus)

Adenocarcinoma

ESOPHAGUS ______ • Clinical features: Caucasian males. Rapid increase in incidence since 1970s. Patients usually present with pain or dysphagia, progressive weight loss, haemetemesis, chest pain or vomiting.

Adenocarcinoma

ESOPHAGUS ______ • 50% in middle third of oesophagus

Squamous cell carcinoma

ESOPHAGUS ______ • Risk factors: Alcohol and tobacco use, poverty, caustic oesophageal injury, achalasia, frequent consumption of very hot beverages, diets deficient in fruits or vegetables, nutritional deficiencies, mutagenic compounds e.g. nitrosamines and polycylic hydrocarbons, HPV infection in high risk areas

Squamous cell carcinoma

ESOPHAGUS ______ • Gross: Small grey-white plaque-like thickenings, growing into tumour masses that may be polypoid/exophytic, protruding and obstructing the lumen. Also may be ulcerative or diffusely infiltrative lesions, causing thickening, rigidity and luminal narrowing. Rich lymphatic network promotes circumferential and longitudinal spread; tumour nodules may present several cm away from the principal mass

Squamous cell carcinoma

ESOPHAGUS ______ • Histology: Begins as in-situ lesion (squamous dysplasia carcinoma in-situ). Most SqCC are well to moderately differentiated.

Squamous cell carcinoma

STOMACH 4 major anatomic regions:

Cardia, fundus, body, antrum.

STOMACH ______ and ______: mucin-secreting foveolar cells that form small glands. ______ also contain endocrine ______ that release gastrin to stimulate luminal acid secretion by parietal cells in the body and fundus

Cardia, antrum, Antral glands, G cells

STOMACH ______ and ______: acid-secreting parietal cells (also secretes ______) and digestive enzymes-secreting chief cells (______)

Body, fundus, intrinsic factor, oxyntic mucosa

STOMACH Normal gastric lumen is extremely ______ (pH close to ______), which contributes to digestion but has potential to damage mucosa

acidic, 1

STOMACH Clinical presentations:

asymptomatic, epigastric pain, nausea, vomiting, haematemesis, melena

STOMACH:

• Gastropathy and acute gastritis • Chronic gastritis • Helicobacter pylori gastritis • Peptic ulcer disease (PUD) • Stress-related mucosal disease • Dysplasia • Polyps • Gastric adenocarcinoma • Lymphoma • Well-differentiated Neuroendocrine Tumours (NET) • Gastrointestinal stromal tumour (GIST)

STOMACH Gastropathy and acute gastritis • ______ = mucosal inflammation. ______ = neutrophils present

Gastritis, Acute gastritis

STOMACH Gastropathy and acute gastritis • ______ = gastric dysfunction or injury with rare or absent inflammatory cells. Causes: NSAIDs, alcohol, bile, stress-induced, portal hypertension.

Gastropathy

STOMACH Gastropathy and acute gastritis • ______: specific group of diseases including ______ and ______

Hypertrophic gastropathy, Menetrier disease, Zollinger-Ellison syndrome

STOMACH ______ • Causes: Chemical e.g. alcohol, bile reflux (post-gastrectomy), corrosives, chemotherapy; radiation therapy; NSAIDs; corticosteroids. Contributory factors: Smoking, elderly age (?due to reduced mucin and bicarbonate secretion), high altitudes (decreased oxygen)

Gastropathy and acute gastritis

STOMACH ______ • Pathogenesis: Disruption of the normal protective mechanisms in the stomach

Gastropathy and acute gastritis

STOMACH Gastropathy and acute gastritis • Pathogenesis: Disruption of the normal protective mechanisms in the stomach ______: mucin secretion by surface foveolar cells forms a thin layer of ______ and ______ that prevents large food particles from directly touching the epithelium

Mucus barrier, mucus, phospholipids

STOMACH Gastropathy and acute gastritis • Pathogenesis: Disruption of the normal protective mechanisms in the stomach ______: the mucus layer has a ______ pH as a result of bicarbonate ion secretion by surface epithelial cells

Bicarbonate secretion, neutral

STOMACH Gastropathy and acute gastritis • Pathogenesis: Disruption of the normal protective mechanisms in the stomach ______: the gastric epithelial cells beneath the mucus layer has intercellular tight junctions, forming a physical barrier that limits back-diffusion of acid and leakage of other luminal materials, including ______, into the ______. The epithelial layer is maintained by complete replacement of the surface ______ every ______ to ______ days

Epithelial barrier, pepsin, lamina propria, foveolar cells, 3, 7

STOMACH Gastropathy and acute gastritis • Pathogenesis: Disruption of the normal protective mechanisms in the stomach ______: delivers bicarbonate, oxygen and nutrients to epithelial cells while washing away acid that has back-diffused into the lamina propria. In acid-secreting parts of the stomach, a capillary ‘______’ is generated as ______ secrete ______ into the gastric lumen and bicarbonate into the vessels

Rich mucosal blood flow, alkaline tide, parietal cells, hydrochloride acid

STOMACH ______ • Histology: foveolar hyperplasia, lamina propria oedema and vascular congestion. Neutrophils seen in ______ (vs ‘gastropathy’). ______ = erosions (superficial mucosal defect due to loss of epithelium) in more severe mucosal damage +/- haemorrhage. Extensive erosions may progress to ______

Gastropathy and acute gastritis, acute gastritis, Acute erosive haemorrhagic gastritis, ulcers

STOMACH ______ • Chronic mucosal inflammation that can lead to mucosal atrophy and intestinal metaplasia (IM)

Chronic gastritis

STOMACH ______ • Causes: Most common - ______ (longstanding can result in atrophic, usually multifocal, gastritis). Others - ______ (most common cause of diffuse atrophic gastritis), radiation injury, chronic bile reflux, mechanical injury, involvement by systemic diseases e.g. Crohn disease, amyloidosis, graft vs host disease

Chronic gastritis, Helicobacter pylori infection, autoimmune gastritis

STOMACH ______ • Clinical presentation: Symptoms usually less severe but more persistent compared to acute gastritis. Nausea, abdominal pain, +/- vomiting. Haematemesis is uncommon.

Chronic gastritis

STOMACH ______ • Complications: ______, ______ which is associated with intestinal metaplasia (IM) and a risk factor to gastric adenocarcinoma (greatest in autoimmune gastritis, possibly because achlorhydia of gastric mucosal atrophy permits overgrowth of bacteria that produce carcinogenic nitrosamines. IM in chronic H.pylori gastritis may regress after clearance of the organisms)

Chronic gastritis, Peptic ulcer disease, mucosal atrophy

STOMACH ______ • Spiral-shaped or curved bacilli that causes predominantly antral gastritis with normal or increased (local) gastrin production

Helicobacter pylori gastritis

STOMACH ______ • Pathogenesis: Pattern of this is a result of interplay between gastroduodenal mucosal defenses, host inflammatory responses and bacterial virulence factors.

Helicobacter pylori gastritis

STOMACH Helicobacter pylori gastritis • There is an inverse relationship between risk of duodenal ulcer and gastric adenocarcinoma depending on the pattern:

1. Antral-limited 2. Pangastritis

STOMACH Helicobacter pylori gastritis • There is an inverse relationship between risk of duodenal ulcer and gastric adenocarcinoma depending on the pattern ______: Greater risk of duodenal peptic ulcer due to the increased acid production (due to stimulation of gastrin release by cytokines released or specific products of H.pylori)

Antral-limited

STOMACH Helicobacter pylori gastritis • There is an inverse relationship between risk of duodenal ulcer and gastric adenocarcinoma depending on the pattern ______: Body and fundus progressively involved, resulting in multifocal atrophic gastritis associated with reduced parietal cell mass and acid secretion, IM and increased risk of gastric adenocarcinoma

Pangastritis

STOMACH Helicobacter pylori gastritis • Virulence of H.pylori is linked to several factors:

• Flagella • Urease • Adhesins • Toxins

STOMACH Helicobacter pylori gastritis • Virulence of H.pylori is linked to several factors ______: allows the bacteria to be motile in viscous mucus

Flagella

STOMACH Helicobacter pylori gastritis • Virulence of H.pylori is linked to several factors ______: generates ammonia from endogenous urea and thereby elevates local gastric pH and enhances bacterial survival

Urease

STOMACH Helicobacter pylori gastritis • Virulence of H.pylori is linked to several factors ______: enhance bacterial adherence to surface foveolar cells

Adhesins

STOMACH Helicobacter pylori gastritis • Virulence of H.pylori is linked to several factors ______: cytotoxin-associated gene A (CagA) and the associated 20 gene pathogenicity islands that are present in 50% of H.pylori isolates overall but 90% in populations with elevated gastric cancer risk and therefore may be involved in disease progression, partly because CagA expressing strains can effectively colonize the gastric body and cause multifocal atrophic gastritis

Toxins

STOMACH Helicobacter pylori gastritis • Host factors:

• Genetic polymorphisms that lead to increased expression of proinflammatory cytokines tumour necrosis factor (TNF) and interleukin IL-1b or decreased expression of the anti-inflammatory cytokine IL-10 are associated with development of pangastritis, atrophy and gastric cancer. • Iron deficiency may also be risk factor of H.pylori associated gastric cancer

STOMACH ______ • Histology: H.pylori organisms within the superficial mucus overlying the epithelial cells in the surface and neck regions (has tropism for gastric epithelia, not found in areas of IM or duodenal epithelium). Can be demonstrated with special stain

Helicobacter pylori gastritis

STOMACH ______ • Chronic mucosal ulceration affecting the duodenum or stomach, usually due to H.pylori infection

Peptic ulcer disease (PUD)

STOMACH Peptic ulcer disease (PUD):

• Antrum/proximal duodenum (most common location) • Body/fundus • Oesophagus (rare)

STOMACH Peptic ulcer disease (PUD) • ______: usually due to chronic H.pylori induced antral gastritis, which is associated with increased acid secretion and decreased duodenal bicarbonate secretion

Antrum/proximal duodenum (most common location)

STOMACH Peptic ulcer disease (PUD) • ______: usually due to some H.pylori gastritis or AI gastritis, resulting in mucosal atrophy and lesser acid secretion. Therefore protects from antral/duodenal ulcers

Body/fundus

STOMACH Peptic ulcer disease (PUD) • ______: due to GERD or acid secretion by ectopic gastric mucosa (can occur occur in duodenum or Meckel diverticulum)

Oesophagus (rare)

STOMACH ______ • Pathogenesis: Imbalance between mucosal defenses and damaging factors of chronic gastritis (PUD therefore generally develops on a background of chronic gastritis). Likely host and bacterial factors determine why some people develop only chronic gastritis and others get PUD

Peptic ulcer disease (PUD)

STOMACH ______ • Clinical features: Most due to H.pylori infection, NSAIDs (potentiated by steroids) or cigarette smoking (synergizes with H.pylori for gastric PUD). Rare causes e.g. Zollinger-Ellison syndrome

Peptic ulcer disease (PUD)

STOMACH ______ • Presentation: Epigastric burning or aching pain (can be chronic/recurring, occurring 1-3hrs after meals, worse at night and relieved by alkali or food).

Peptic ulcer disease (PUD)

STOMACH ______ • Complications: Bleeding (most frequent - ______-______% of patients; may be life threatening or first presentation); Perforation (______%; accounts for ______ of ulcer deaths – surgical emergency!);

Peptic ulcer disease (PUD), 15, 20, 5, 2/3

STOMACH ______ • Obstruction Treatment: H.pylori eradication, neutralization of gastric acid (primarily with proton pump inhibitors (PPI)), and withdrawal of offending agents

Peptic ulcer disease (PUD)

STOMACH ______ • Gross: Solitary (>80%), round to oval, sharply punched-out defect with a smooth clean ulcer base as a result of peptic digestion of exudate.

Peptic ulcer disease (PUD)

STOMACH ______ • Histology: thin surface layer of fibrinopurulent exudate, underlying suppurative necrosis, granulation tissue with mononuclear leukocytes, and a fibrocollagenous scar forming the ulcer base. Vessel walls are thickened and possibly thrombosed within the scarred area – bleeding from these damaged vessels from the ulcer base may cause life-threatening haemorrhage.

Peptic ulcer disease (PUD)

STOMACH ______ • Occurs in patients with severe physiologic stress, usually during the 1st 3 days (acute)

Stress-related mucosal disease

STOMACH Stress-related mucosal disease:

• Stress ulcers • Curling ulcers • Cushing ulcers

STOMACH Stress-related mucosal disease • ______: shock, sepsis, severe trauma, post-myocardial infarction

Stress ulcers

STOMACH Stress-related mucosal disease • ______: severe burns or trauma. Proximal duodenum

Curling ulcers

STOMACH Stress-related mucosal disease • ______: intracranial disease. Duodenum and oesophagus. High incidence of perforation

Cushing ulcers

STOMACH ______ • Healing with complete re-epithelisation occurs within days to several weeks after correction of the underlying condition

Stress-related mucosal disease

STOMACH ______ • Pathogenesis: Local ischaemia from systemic hypotension or stress-induced splanchnic vasoconstriction, upregulation of inducible nitric oxide synthase and increased release of vasoconstrictor endothelin-1.

Stress-related mucosal disease

STOMACH ______ • Gross: shallow erosions to deeper ulcers anywhere in stomach, usually multiple, rounded and less than 1 cm in size. Ulcer base frequently stained brown to black by acid digestion of extravasated blood

Stress-related mucosal disease

STOMACH ______ • Histology: erosion/ulcer sharply demarcated with adjacent normal mucosa. No scarring or blood vessel thickening seen in peptic ulcers (which arise in the setting of chronic injury). (neuroendocrine cell hyperplasia tumour)

Stress-related mucosal disease

STOMACH ______ • Preinvasive in-situ lesion with architectural and cytologic atypia

Dysplasia

STOMACH ______ • Often arises in background of chronic gastritis, which exposes the epithelium to inflammation-related free radical damage and proliferative stimuli that lead to the accumulation of genetic alterations over time that result in carcinoma

Dysplasia

STOMACH ______ • Develop due to epithelial or stromal cell hyperplasia, inflammation, ectopia or neoplasia.

Polyps

STOMACH Polyps:

• Inflammatory and hyperplastic polyps • Fundic gland polyps • Gastric adenoma

STOMACH Polyps • ______: 75% of all gastric polyps. Reactive lesions, usually in a/w chronic gastritis which initiates the injury that leads to reactive hyperplasia and polyp growth. Risk of dysplasia correlates with polyp size

Inflammatory and hyperplastic polyps

STOMACH Polyps • ______: sporadic or in patients with familial adenomatous polyposis (FAP). Increasing incidence with use of PPI therapy, which inhibits acid production, thereby increasing gastrin secretion which stimulates oxyntic gland growth. Sporadic polyps have no cancer risk, while FAP-associated polyps may develop dysplasia and cancer

Fundic gland polyps

STOMACH Polyps • ______: 10% of all gastric polyps. Frequency increases with age; prevalence varies and parallels incidence of gastric adenocarcinoma. M:F = ______:______. Incidence also increased in ______ patients. Similar to dysplasia, it occurs on a background of chronic gastritis with atrophy and intestinal metaplasia. Significant risk of adenocarcinoma (up to 30% of adenomas; related to size of lesion) requires more aggressive therapy than colonic adenomas

Gastric adenoma, 3, 1, FAP

STOMACH ______ • More than 90% of all gastric cancers. Malignant epithelial neoplasm with glandular differentiation

Gastric adenocarcinoma

STOMACH Gastric adenocarcinoma • Two main (Lauren) histologic subtypes:

Intestinal-type and diffuse-type

STOMACH Gastric adenocarcinoma • Two main (Lauren) histologic subtypes ______: Predominates in high-risk areas (e.g. Japan, East Europe). Precursor lesions include flat dysplasia and adenoma. M:F = ______:______

Intestinal-type, 2, 1

STOMACH Gastric adenocarcinoma • Two main (Lauren) histologic subtypes ______: Incidence is relatively uniform across countries, with no clearly identified precursor lesions. ______=______.

Diffuse-type, M, F

STOMACH ______ • Pathogenesis: Majority are sporadic; familial gastric cancers tend to be diffuse-type.

Gastric adenocarcinoma

STOMACH Gastric adenocarcinoma • Pathogenesis ______: Loss of expression of cell adhesion protein E-cadherin is a key step. This may occur via loss of function mutations in the tumour suppressor gene CDH1 which encodes E- cadherin (germline loss is strongly associated in familial gastric cancer, but loss of function is also seen in ~50% of sporadic diffuse-type tumours).

Diffuse-type

STOMACH Gastric adenocarcinoma • Pathogenesis ______: Strongly associated with mutations that result in increased signaling via the Wnt pathway, including loss-of-function mutations in the adenomatous polyposis coli (APC) tumour suppressor gene and gain-of-function mutations in the gene encoding b-catenin.

Intestinal-type

STOMACH ______ • Clinical features: Early symptoms are usually non-specific (e.g. dyspepsia, nausea, dysphagia). Tumours are therefore often diagnosed at late stage with weight loss, anorexia and haemorrhage.

Gastric adenocarcinoma

STOMACH ______ • Prognosis: depends on depth of tumour invasion (e.g. into adjacent organs), extent of nodal and distant metastases. Favourite sites of metastases: ______ (______), ______ (______), ______ (______), ______ (______).

Gastric adenocarcinoma, supraclavicular LN, Virchow node, periumbilical LN, Sister Mary Joseph nodule, ovary, Krukenberg tumour, pouch of Douglas, Blumer shelf

STOMACH ______ • Gross: mostly antrum (______ > ______)

Gastric adenocarcinoma, lesser curve, greater curve

STOMACH Gastric adenocarcinoma • Gross ______: usually bulky exophytic masses or ulcers/excavated

Intestinal-type

STOMACH Gastric adenocarcinoma • Gross ______: usually flat/depressed, widely infiltrative, inducing stromal desmoplasia that thickens and stiffens the gastric wall and causes rugal flattening, imparting a leather bottle appearance (‘______’), rather than forming a discrete tumour mass

Diffuse-type, linitis plastica

STOMACH Gastric adenocarcinoma • Histology ______: glandular structures with apical and luminal mucin

Intestinal-type

STOMACH Gastric adenocarcinoma • Histology ______: discohesive cells that infiltrate singly or in small clusters and do not form glands; may have ‘signet-ring cell’ appearance (i.e. large intracytoplasmic mucin vacuole that pushes the nucleus to the periphery

Diffuse / poorly cohesive-type

STOMACH ______ • Extranodal lymphomas arise commonly in the GI tract, especially the stomach. ~5% of all gastric malignancies are primary lymphomas, most commonly ______.

Lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma)

STOMACH ______ • Pathogenesis: MALToma usually arises at sites of chronic inflammation - ______ is the most common inducer of MALT lymphoma in the stomach

Lymphoma, H.pylori infection

STOMACH ______ • Clinical presentation: dyspepsia, epigastric pain +/- haematemesis, melena and constitutional symptoms.

Lymphoma

STOMACH ______ • Histology: dense lymphoid infiltrate in the lamina propria, which infiltrates gastric glands to form lymphoepithelial lesions. Expresses B cell marker ______, negative for ______ and ______

Lymphoma, CD20, CD5, CD10

STOMACH ______ • Previously known as carcinoid or ‘carcinoma-like’ tumours as they have a more indolent clinical course than GI carcinomas; more than ______% of GI NET occur in the small intestine

Well-differentiated Neuroendocrine Tumours (NET), 40

STOMACH ______ • Clinical presentation: Asymptomatic or symptomatic depending on the hormones produced e.g. gastrin-secreting tumours may cause ______, while ileal tumours may cause ______ (cutaneous flushing, sweating, bronchospasm, diarrhoea etc. due to released substances including serotonin) especially in the presence of metastatic liver disease (whereby the bioactive products are directly released into the systemic circulation without the ‘first-pass effect’) or with a large enough tumour burden.

Well-differentiated Neuroendocrine Tumours (NET), Zollinger-Ellison syndrome, carcinoid syndrome

STOMACH ______ • Gross: Intramural or submucosal masses that create small polypoid yellow-tan lesions. Often firm (due to desmoplastic reaction) can cause kinking and small bowel obstruction

Well-differentiated Neuroendocrine Tumours (NET)

STOMACH ______ • Histology: Islands, trabeculae, strands, glands or sheets of uniform cells with round to oval nucleus, ‘salt and pepper’ chromatin and scant pink cytoplasm. Positive with immunohistochemical stains for neuroendocrine granule markers e.g. Synaptophysin and Chromogranin A

Well-differentiated Neuroendocrine Tumours (NET)

STOMACH ______ • Most common mesenchymal tumour of the abdomen arising from interstitial cells of Cajal of the muscularis propria; more than ______% occur in the stomach

Gastrointestinal stromal tumour (GIST), 50

STOMACH ______ • Pathogenesis: ~______-______% have oncogenic gain-of-function mutations in the tyrosine kinase receptor (TKR) KIT, while ~______% have activating mutations in a closely related TKR, platelet-derived growth factor receptor α (PDGFRA)

Gastrointestinal stromal tumour (GIST), 75, 80, 8

STOMACH ______ • Clinical features: Usually in adults ~60 yo, uncommonly in children (some of which are related to ______, a nonhereditary syndrome seen primarily in young females that includes gastric GIST, paraganglioma and pulmonary chondroma, or ______). Patients can be asymptomatic or symptomatic related to mass effect or mucosal ulceration causing blood loss/anemia.

Gastrointestinal stromal tumour (GIST), Carney triad, Neurofibromatosis (NF) type 1

STOMACH ______ • Gross: usually solitary, well-circumscribed fleshy mass covered by ulcerated or intact mucosa; may also bulge out towards serosa. Cut surface has a whorled appearance

Gastrointestinal stromal tumour (GIST)

STOMACH ______ • Histology: Spindle cell or epithelioid type or mixed. Immunohistochemical expression of ______/______ (detectable even for those without the mutation) or ______

Gastrointestinal stromal tumour (GIST), KIT, CD117, DOG1

______ • Main functions: Nutrient and water transport

SMALL INTESTINE AND COLON

______ • dysfunction causes malabsorption and diarrhoea

SMALL INTESTINE AND COLON

______ • Immune system interfaces with a diverse array of antigens present in food and gut microbes; infectious and inflammatory disorders

SMALL INTESTINE AND COLON

SMALL INTESTINE AND COLON ______ is also a frequent site of gastrointestinal tumours

Colon

SMALL INTESTINE AND COLON:

• Intestinal obstruction • Ischaemic bowel disease • Necrotizing enterocolitis (NEC • Angiodysplasia • Malabsorption and diarrhoea • Cystic fibrosis • Lactase (disaccharidase) deficiency • Inflammatory bowel disease (IBD) • Diverticular disease • Polyps • Colorectal cancer syndromes • Colorectal adenocarcinoma (CRC)

SMALL INTESTINE AND COLON ______ • Can occur at any level, but frequently small intestine because of its relatively narrow lumen

Intestinal obstruction

SMALL INTESTINE AND COLON ______ • Causes: Hernias (most frequent cause worldwide), intestinal adhesions, intussusception, volvulus, and more rarely, tumours, infarction and other causes of strictures e.g. Crohn disease

Intestinal obstruction

SMALL INTESTINE AND COLON ______ • Clinical presentation: abdominal pain and distension, vomiting and constipation. May be complicated by bowel perforation; surgical emergency

Intestinal obstruction

SMALL INTESTINE AND COLON Intestinal obstruction • ______: protrusion of a serosa-lined pouch of peritoneum through any weakness or defect in the abdominal wall

Hernia sac

SMALL INTESTINE AND COLON Intestinal obstruction • ______: fibrous bridges that can develop between bowel segments, abdominal wall or other sites. Usually acquired (e.g. due to previous surgery, infection or other causes of peritoneal inflammation e.g. endometriosis) but can rarely be congenital.

Adhesions

SMALL INTESTINE AND COLON Intestinal obstruction • ______: twisting of a loop of bowel about its mesenteric point of attachment, resulting in both luminal and vascular compromise

Volvulus

SMALL INTESTINE AND COLON Intestinal obstruction • ______: when a segment of intestine, constricted by a wave of peristalsis, telescopes into the immediately distal segment. Once trapped, the invaginated segment is further propelled by peristalsis and pulls the mesentery along. May progress to intestinal obstruction as well as compression of mesenteric vessels (infarction). Most common cause of IO in children <______yo

Intussusception, 2

SMALL INTESTINE AND COLON ______ • Majority of GI tract supplied by celiac, superior mesenteric and inferior mesenteric arteries (SMA and IMA), with collateral supplies from the proximal celiac and distal pudendal and iliac circulations. Disease extent depends on (1) ______, (2) ______ (acute compromise vs chronic progressive hypoperfusion) and (3) ______

Ischaemic bowel disease, severity of vascular compromise, the time frame during which it develops, vessels affected

SMALL INTESTINE AND COLON Ischaemic bowel disease • Particularly vulnerable regions of the GIT:

• Intestinal segments at the end of their respective arterial supplies (‘watershed zones’) i.e. splenic flexure (where the SMA and IMA circulations terminate), and rectosigmoid colon • Surface epithelium

SMALL INTESTINE AND COLON ______ • Risk factors: (______) coexisting cardiac or vascular disease, therapeutic vasoconstrictors, some illicit drugs e.g. cocaine, (______) CMV infection causing endothelial damage and small vessel occlusion, strangulated hernia.

Ischaemic bowel disease, systemic, localized

SMALL INTESTINE AND COLON ______ • Pathogenesis: 2 phases - (1) initial hypoxic injury at the onset of vascular compromise (2) reperfusion injury, initiated by restoration of the blood supply.

Ischaemic bowel disease

SMALL INTESTINE AND COLON Ischaemic bowel disease • Pathogenesis: 2 phases:

(1) initial hypoxic injury at the onset of vascular compromise (2) reperfusion injury, initiated by restoration of the blood supply

SMALL INTESTINE AND COLON ______ • Clinical features: Elderly patients, slightly more women. ______ typically presents with sudden onset of cramping, left lower abdominal pain, a desire to defecate, and bloody diarrhoea. Surgical emergency if there is paralytic ileus or other features of infarction e.g. guarding and rebound tenderness; can be complicated by gram-negative bacteraemia (endotoxic shock) or perforation. ______ may mimic inflammatory bowel disease, with episodes of bloody diarrhoea interspersed with periods of healing

Ischaemic bowel disease, Acute ischaemia, Chronic ischaemia

SMALL INTESTINE AND COLON ______ • Gross: lesions are most often segmental and patchy. Major vessel occlusions tends to cause transmural infarction, while hypoperfusion / partial occlusion cause mucosal / mural infarction only. Mucosa haemorrhagic and may be ulcerated, while the bowel wall is thickened by oedema

Ischaemic bowel disease

SMALL INTESTINE AND COLON ______ • Histology: atrophy or sloughing of surface epithelium, with normal or hyperproliferative crypts. Bacterial superinfection and enterotoxin release may also induce pseudomembrane formation (resembling Clostridium difficile-associated pseudomembranous colitis).

Ischaemic bowel disease

SMALL INTESTINE AND COLON Ischaemic bowel disease • Histology ______: Inflammation initially absent, but neutrophils are recruited within hours of reperfusion.

Acute ischaemia

SMALL INTESTINE AND COLON Ischaemic bowel disease • Histology ______: Accompanied by fibrous scarring / hyalinization of the lamina propria, and (rarely) stricture formation

Chronic ischaemia

SMALL INTESTINE AND COLON ______ • acute disorder of small and large intestines that can result in transmural necrosis, possibly partly due to ischaemic injury. Most common acquired GI emergency of neonates

Necrotizing enterocolitis (NEC)

SMALL INTESTINE AND COLON ______ • Lesion characterized by malformed submucosal and mucosal blood vessels, most often in the caecum or right colon, and usually presents after ______yo. Low incidence but accounts for ______% of major episodes of lower intestinal bleeding; may be chronic and intermittent or acute and massive

Angiodysplasia, 50, 20

SMALL INTESTINE AND COLON ______ • Pathogenesis: attributed to mechanical and congenital factors. Normal distension and contraction may intermittently occlude the submucosal veins that penetrate through the muscularis propria and lead to focal dilatation and tortuosity of overlying submucosal and mucosal vessels.

Angiodysplasia

SMALL INTESTINE AND COLON ______ • Histology: ectatic nests of tortuous veins, venules and capillaries, which may be separated from the intestinal lumen by only the vascular wall and a layer of attenuated epithelial cells; can be easily traumatized resulting in significant bleeding

Angiodysplasia

SMALL INTESTINE AND COLON Malabsorption and diarrhoea ______ • defective absorption of fat, fat- and water-soluble vitamins, proteins, carbohydrates, electrolytes, minerals, and water, presenting most commonly as chronic diarrhoea

Malabsorption

SMALL INTESTINE AND COLON Malabsorption and diarrhoea ______ • Causes: pancreatic insufficiency, celiac disease, Crohn disease, intestinal graft-vs-host disease

Malabsorption

SMALL INTESTINE AND COLON Malabsorption and diarrhoea ______ • Clinical symptoms: ______ (hallmark - excessive fecal fat and bulky frothy greasy yellow or clay-coloured stools), weight loss, flatus, anorexia, abdominal distension/pain, muscle wasting, symptoms of vitamin deficiency e.g. anaemia (B12 deficiency), bleeding (vitamin K deficiency) etc.

Malabsorption, Steatorrhoea

SMALL INTESTINE AND COLON Malabsorption and diarrhoea ______ • increase in stool mass, frequency or fluidity, typically greater than 200g per day.

Diarrhoea

SMALL INTESTINE AND COLON Malabsorption and diarrhoea Diarrhoea • ______: painful, bloody, small-volume diarrhoea

Dysentery

SMALL INTESTINE AND COLON Malabsorption and diarrhoea Diarrhoea • ______: isotonic stool; persists during fasting

Secretory

SMALL INTESTINE AND COLON Malabsorption and diarrhoea Diarrhoea • ______: due to excessive osmotic forces exerted by unabsorbed luminal solutes e.g. with lactase deficiency. Diarrhoea fluid is more concentrated than plasma (hypertonic); abates with fasting

Osmotic

SMALL INTESTINE AND COLON Malabsorption and diarrhoea Diarrhoea • ______: generalized failure of nutrient absorption, a/w steatorrhoea; relieved by fasting

Malabsorptive

SMALL INTESTINE AND COLON Malabsorption and diarrhoea Diarrhoea • ______: due to inflammatory disease, characterized by purulent bloody stools; continues during fasting

Exudative

SMALL INTESTINE AND COLON Malabsorption and diarrhoea Diarrhoea:

• Dysentery • Secretory • Osmotic • Malabsorptive • Exudative

SMALL INTESTINE AND COLON ______ • Defect in chloride (+/- bicarbonate ion) secretion due to the absence of the epithelial cystic fibrosis transmembrane conductance regulator (CFTR), resulting in defective luminal hydration and thickened secretions. Pancreatic intraductal concretions can form, causing duct obstruction, low grade chronic autodigestion of the pancreas and eventual exocrine pancreatic insufficiency; malabsorptive diarrhoea

Cystic fibrosis

SMALL INTESTINE AND COLON ______ • Treatment = oral enzyme supplementation

Cystic fibrosis

SMALL INTESTINE AND COLON ______ • Osmotic diarrhoea due to inability to break down or absorb lactase. Can be congenital (rare autosomal recessive disorder caused by mutation in gene encoding lactase) or acquired (common in adults, caused by down-regulation of lactase gene expression, which can develop following enteric viral or bacterial infections and may resolve over time). Defect is biochemical so histology is generally unremarkable

Lactase (disaccharidase) deficiency

SMALL INTESTINE AND COLON ______ • Chronic inflammation of the GI tract resulting from inappropriate mucosal immune activation, usually referring to either ______ or ______

Inflammatory bowel disease (IBD), Ulcerative Colitis (UC), Crohn Disease (CD)

SMALL INTESTINE AND COLON ______ • Pathogenesis: Likely due to combined effects of alterations in host interactions with intestinal microbiota, intestinal epithelial dysfunction, aberrant mucosal immune responses and altered

Inflammatory bowel disease (IBD)

SMALL INTESTINE AND COLON ______ • Clinical features: Teens and young adults. Caucasians but increasing incidence in other regions e.g. Africa, South America and Asia. Distinction between CD and UC is based largely on the ______ and ______ at these sites. ______ may also be present.

Inflammatory bowel disease (IBD), distribution of affected sites, morphologic expression of disease, Extraintestinal manifestations

SMALL INTESTINE AND COLON Inflammatory bowel disease (IBD) Crohn disease or Ulcerative colitis? • Recurrent granulomatous, fibrosing inflammatory disorder affecting terminal ileum (or colon) +/- other systemic manifestations

Crohn disease

SMALL INTESTINE AND COLON Inflammatory bowel disease (IBD) Crohn disease or Ulcerative colitis? • Recurrent acute-on-chronic ulcero-inflammatory disease affecting mainly rectum and distal colon

Ulcerative colitis

SMALL INTESTINE AND COLON Inflammatory bowel disease (IBD) Crohn disease or Ulcerative colitis? • Clinical features: Relapsing disorder: intermittent attacks of (bloody) diarrhoea with stringy mucoid material, lower abdominal pain, cramps that are temporarily relieved by defecation +/- fever; can also present acutely. Asymptomatic periods may last for weeks to months

Both

SMALL INTESTINE AND COLON Inflammatory bowel disease (IBD) Crohn disease or Ulcerative colitis? • Clinical features: Disease re-activation by triggers include physical or emotional stress, specific dietary items and cigarette smoking (a strong exogenous risk factor for development of Crohn disease; initiation of smoking may be associated with disease onset but smoking cessation does not result in disease remission)

Crohn disease

SMALL INTESTINE AND COLON Inflammatory bowel disease (IBD) Crohn disease or Ulcerative colitis? • Clinical features: Triggers may include episode of infectious enteritis, psychological stress, after smoking cessation

Ulcerative colitis

SMALL INTESTINE AND COLON Inflammatory bowel disease (IBD) Crohn disease or Ulcerative colitis? • Clinical features: Extraintestinal manifestations: uveitis, ankylosing spondylitis, migratory polyarthritis

Crohn disease

SMALL INTESTINE AND COLON Inflammatory bowel disease (IBD) Crohn disease or Ulcerative colitis? • Clinical features: Similar; also primary sclerosing cholangitis (PSC)

Ulcerative colitis

SMALL INTESTINE AND COLON Inflammatory bowel disease (IBD) Crohn disease or Ulcerative colitis? • Clinical features: Saccharomyces cerevisiae antibodies positive

Crohn disease

SMALL INTESTINE AND COLON Inflammatory bowel disease (IBD) Crohn disease or Ulcerative colitis? • Clinical features: pANCA+ (75%)

Ulcerative colitis

SMALL INTESTINE AND COLON Inflammatory bowel disease (IBD) Crohn disease or Ulcerative colitis? • Complications: Fistulae between bowel loops and with other organs e.g. bladder, vagina, skin (esp. perianal); perforations and peritoneal abscesses

Crohn disease

SMALL INTESTINE AND COLON Inflammatory bowel disease (IBD) Crohn disease or Ulcerative colitis? • Complications: Nil

Ulcerative colitis

SMALL INTESTINE AND COLON Inflammatory bowel disease (IBD) Crohn disease or Ulcerative colitis? • Complications: Fibrosing strictures (particularly of the terminal ileum; require surgical resection)

Crohn disease

SMALL INTESTINE AND COLON ______ • Occurs secondary to donor T cells targeting antigens on the recipient’s GI epithelial cells. Histology shows epithelial apoptosis (particularly of the crypt cells) with sparse inflammation in the lamina propria. Rarely, total gland destruction occurs

Inflammatory bowel disease (IBD)

SMALL INTESTINE AND COLON ______ • Acquired pseudodiverticular outpouchings of colonic mucosa and submucosa (unlike true diverticula e.g. Meckel diverticulum, which includes all 3 layers of the colonic wall). Usually multiple (______)

Diverticular disease, diverticulosis

SMALL INTESTINE AND COLON ______ • Pathogenesis: results from the elevated intraluminal pressure usually in the sigmoid colon (probably due to exaggerated peristaltic contractions with spasmodic sequestrations of bowel segments, which may be enhanced by diets low in fiber which reduce stool bulk, particularly in the sigmoid colon). This causes outpouchings in the focal discontinuities in the colonic muscle wall where nerves, arterial vasa recta and their connective tissue sheaths penetrate the inner circular muscular coat. The external longitudinal layer of the MP is unable to reinforce these gaps as they are gathered into the 3 bands (______) in the colon

Diverticular disease, taenia coli

SMALL INTESTINE AND COLON ______ • Clinical features: Most individuals are asymptomatic, but ~20% present with intermittent cramping, continuous lower abdominal discomfort, constipation, distension, sensation of incomplete defecation or occasionally chronic / intermittent per rectal bleeding (with erosion into blood vessels).

Diverticular disease

SMALL INTESTINE AND COLON ______ • Gross: small flask-like outpouchings ~______-______ cm in diameter that occur alongside the taenia coli

Diverticular disease, 0.5, 1

SMALL INTESTINE AND COLON ______ • Histology: thin wall composed of flattened / atrophic mucosa, compressed submucosa and attenuated or totally absent muscularis propria. Hypertrophy of the circular layer of the muscularis propria in the affected bowel segment is common

Diverticular disease

SMALL INTESTINE AND COLON ______ • Gross morphology: ______ (broad-based) vs ______ (narrow base +/- stalk)

Polyps, sessile, pedunculated

SMALL INTESTINE AND COLON ______ • ______ (inflammatory, hamartomatous or hyperplastic) vs ______ (usually adenoma)

Polyps, Non-neoplastic, neoplastic

SMALL INTESTINE AND COLON Polyps Non-neoplastic polyps:

• Hyperplastic • Inflammatory • Hamartomatous

SMALL INTESTINE AND COLON Polyps Non-neoplastic polyps • ______: benign epithelial proliferations, usually in left colon, often multiple. Serrated surface architecture (serrations restricted to upper third of the crypt)

Hyperplastic

SMALL INTESTINE AND COLON Polyps Non-neoplastic polyps • ______: can form as part of the solitary rectal ulcer syndrome due to impaired relaxation of the anorectal sphincter, leading to recurrent abrasion and ulceration of the overlying rectal mucosa; an inflammatory polyp develops as a result of the chronic cycles of injury and healing. Entrapment of the polyp in the fecal stream subsequently leads to mucosal prolapse.

Inflammatory

SMALL INTESTINE AND COLON Polyps Non-neoplastic polyps • ______: Histology = mixed inflammatory infiltrates, surface erosion, and epithelial hyperplasia +/- lamina propria fibromuscular hyperplasia (in mucosal prolapse)

Inflammatory

SMALL INTESTINE AND COLON Polyps Non-neoplastic polyps • ______: occur sporadically or as part of various genetically determined or acquired syndromes (some of which are associated with increased cancer risk either within the polyps or at other intestinal or extra-intestinal sites)

Hamartomatous

SMALL INTESTINE AND COLON Polyps ______ • any neoplastic mass lesion in the GI tract may produce a mucosal protrusion or polyp, including adenocarcinoma, neuroendocrine tumours, stromal tumours, lymphomas and even metastatic cancers from distant sites. Most common neoplastic polyps are ______, which are precursors to the majority of colorectal adenocarcinomas

Neoplastic, colonic adenomas

SMALL INTESTINE AND COLON Polyps Neoplastic • ______ are intraepithelial neoplasms, ranging from small often pedunculated polyps to large sessile lesions, characterized by the presence of ______. ______ is characterized by cytologic and architectural atypia, and can be low grade or high grade

Adenomas, epithelial dysplasia, Dysplasia

SMALL INTESTINE AND COLON ______ • ______ like FAP and non-polyposis syndromes like HNPCC typify distinct pathways of neoplastic transformation and progression that also contribute to the majority of sporadic colon cancers

Colorectal cancer syndromes, Adenomatous polyposis syndromes

SMALL INTESTINE AND COLON Colorectal cancer syndromes Adenomatous polyposis:

• Familial adenomatous polyposis (FAP) • Hereditary non-polyposis colorectal cancer (HNPCC) / Lynch Syndrome (LS)

SMALL INTESTINE AND COLON Colorectal cancer syndromes Adenomatous polyposis ______ • AD disorder in which patients develop numerous colorectal adenomas as teenagers, caused by mutations of the ______ gene in ______, a key negative regulator of the Wnt signaling pathway. Classic FAP require at least 100 polyps.

Familial adenomatous polyposis (FAP), adenomatous polyposis coli (APC), chr5q21

SMALL INTESTINE AND COLON Colorectal cancer syndromes Adenomatous polyposis ______ • Most common syndromic form of colon cancer (______-______% of all colorectal cancers)

Hereditary non-polyposis colorectal cancer (HNPCC) / Lynch Syndrome (LS), 2, 4

SMALL INTESTINE AND COLON Colorectal cancer syndromes Adenomatous polyposis ______ • AD; caused by inherited mutations in genes that encode mismatch repair proteins (MMR) (responsible for the detection, excision and repair of errors that occur during DNA replication). Defects in mismatch repair lead to the accumulation of mutations at rates up to ______ times higher than normal, mostly in regions containing short repeating sequences referred as ______ (______)

Hereditary non-polyposis colorectal cancer (HNPCC) / Lynch Syndrome (LS), 1000, microsatellites, microsatellite instability

SMALL INTESTINE AND COLON ______ • It is the most common GI tract malignancy and a major cause of morbidity and mortality worldwide (______% of all cancer deaths). In contrast, the small intestine is an uncommon site for benign and malignant tumours despite accounting for ______% of the overall length of the GI tract

Colorectal adenocarcinoma (CRC), 10, 75

SMALL INTESTINE AND COLON ______ • Risk factors: Diet – increased risk with low intake of unabsorbable vegetable fiber and high intake of refined carbohydrates. It is believed that reduced fiber content leads to decreased stool bulk and altered composition of the intestinal microbiota, which may increase synthesis of potentially toxic oxidation by-products of bacterial metabolism

Colorectal adenocarcinoma (CRC)

SMALL INTESTINE AND COLON ______ • ______: epidemiologic studies suggest that aspirin or other NSAIDS have a protective effect, possibly mediated by inhibition of the enzyme ______, which is highly expressed in ______% of colorectal carcinomas and ______-______% of colorectal adenomas. ______ is necessary for production of prostaglandin E2, which promotes epithelial proliferation, particularly after injury

Colorectal adenocarcinoma (CRC), Pharmacologic chemoprevention, cyclooxygenase-2 (COX-2), 90, 40, 90, COX2

SMALL INTESTINE AND COLON ______ • Pathogenesis: heterogeneous combination of molecular events that includes genetic and epigenetic abnormalities, resulting in the stepwise accumulation of multiple mutations.

Colorectal adenocarcinoma (CRC)

SMALL INTESTINE AND COLON Colorectal adenocarcinoma (CRC) • Pathogenesis: At least 2 genetic pathways:

(1) APC/b-catenin pathway (80% of sporadic colon tumours) (2) Microsatellite instability (MSI) pathway

SMALL INTESTINE AND COLON Colorectal adenocarcinoma (CRC) • Pathogenesis: At least 2 genetic pathways ______: activated in the classic adenoma- carcinoma sequence; chromosomal instability is the hallmark (Vogelstein’s hypothesis)

APC/b-catenin pathway (80% of sporadic colon tumours)

SMALL INTESTINE AND COLON Colorectal adenocarcinoma (CRC) • Pathogenesis: At least 2 genetic pathways ______: associated with defects in DNA mismatch repair and accumulation of mutations in microsatellite repeat regions of the genome (MSI-high tumours)

Microsatellite instability (MSI) pathway

SMALL INTESTINE AND COLON ______ • Clinical features: Peaks at 60-70 yo. R-sided colon cancers often present with symptoms of iron-deficiency anaemia (fatigue and weakness) while L-sided colon cancers may product occult bleeding, changes in bowel habits, cramping and left lower quadrant discomfort.

Colorectal adenocarcinoma (CRC)

SMALL INTESTINE AND COLON ______ • Histology: Both right and left-sided colonic adenocarcinomas are similar. Most tumours are composed of irregular glands, typically cribriform architecture (grade of differentiation depends on extent of gland formation), lined by tall columnar cells with dirty necrotic luminal debris. The invasive component elicits a strong desmoplastic response which is responsible for their firm consistency. Some tumours have abundant mucin, and may be composed of signet-ring cells

Colorectal adenocarcinoma (CRC)

ANAL CANAL Anal canal is divided into thirds – the upper zone is lined by ______, the middle third by ______, and the lower third by ______

columnar rectal epithelium, transitional epithelium, stratified squamous epithelium

ANAL CANAL:

• Haemorrhoids • Carcinomas of the anal canal

ANAL CANAL ______ • Thin-walled dilated submucosal vessels (varices) that protrude beneath the anal or rectal mucosa

Haemorrhoids

ANAL CANAL Haemorrhoids • ______: inferior haemorrhoidal plexus located below the anorectal line

External haemorrhoids

ANAL CANAL Haemorrhoids • ______: superior haemorrhoidal plexus within the distal rectum

Internal haemorrhoids

ANAL CANAL Haemorrhoids:

• External haemorrhoids • Internal haemorrhoids

ANAL CANAL ______ • Risk factors: straining at defecation because of constipation, venous stasis of pregnancy, portal hypertension (similar pathogenesis to oesophageal varices – variceal dilations of the anal and perianal venous plexues form collaterals that connect the poral and caval venous systems, thereby relieving the venous hypertension). Usually in older patients (except pregnant ladies).

Haemorrhoids

ANAL CANAL ______ • May have typical ______ (adenocarcinoma) or ______ (squamous cell carcinoma) patterns of differentiation, recapitulating the normal epithelium of the upper or lower thirds of the anal canal, respectively. Pure squamous cell carcinoma of the anal canal is frequently associated with HPV infection, which also causes precursor lesions e.g. condyloma acuminatum.

Carcinomas of the anal canal, glandular, squamous

______ • Normal true diverticulum of the caecum. Prone to acute and chronic inflammation; tumours (adenocarcinoma, neuroendocrine tumours) can also develop here

VERMIFORM APPENDIX

VERMIFORM APPENDIX:

• Acute appendicitis • Tumours of the appendix

VERMIFORM APPENDIX ______ • Acute inflammation of the appendix; most common in adolescents, young adults (lifetime risk ______%)

Acute appendicitis, 7

VERMIFORM APPENDIX ______ • Pathogenesis: thought to be initiated by progressive increases in intraluminal pressure that compromise venous outflow. In ______-______% of cases, acute appendicitis is associated with overt luminal obstruction, usually caused by a small stone-like mass of stool (______) or less commonly, a gallstone, tumour or mass of worms (______).

Acute appendicitis, 50, 80, faecolith, oxyuriasis vermicularis

VERMIFORM APPENDIX ______ • Clinical features: periumbilical pain that subsequently localizes to the right iliac fossa (RIF), associated with nausea, fever, vomiting and mildly elevated peripheral white cell count. Classic physical examination finding is the ______, deep tenderness located 2/3rd of the distance from the umbilicus to the right anterior superior iliac spine (______).

Acute appendicitis, McBurney sign, McBurney point

VERMIFORM APPENDIX ______ • Treatment: Surgery (appendectomy)

Acute appendicitis

VERMIFORM APPENDIX ______ • Gross: Congested turgid oedematous appendix with dull granular erythematous serosa +/- serosal fibrinopurulent exudates. Lumen may contain fecolith or purulent material

Acute appendicitis

VERMIFORM APPENDIX ______ • Histology: mucosal ulceration, transmural acute inflammation (involving muscularis propria) +/- focal abscesses within the wall (______), subserosal vascular congestion, acute serositis and serosal fibrinopurulent reaction. Further compromise of appendiceal vessels leads to large areas of haemorrhagic ulceration and gangrenous necrosis that extends to the serosa (______), which can be followed by rupture and suppurative peritonitis

Acute appendicitis, acute suppurative appendicitis, acute gangrenous appendicitis

VERMIFORM APPENDIX ______ • Most common tumour is the ______, usually discovered incidentally at the time of surgery or examination of a resected appendix. Usually at the tip of the appendix, with mostly benign behaviour (very infrequent nodal metastasis; distant spread is exceptionally rare)

Tumours of the appendix, well-differentiated neuroendocrine tumour

VERMIFORM APPENDIX ______ • ______ or ______ can also occur in the appendix and may cause obstruction and enlargement that mimics acute appendicitis

Tumours of the appendix, Conventional adenomas, non-mucin-producing adenocarcinomas

VERMIFORM APPENDIX ______ • ______: dilated appendix filled with mucin. This may simply represent an obstructed appendix containing inspissated mucin, or be a consequence of a low grade appendiceal mucinous neoplasm (LAMN) or mucinous adenocarcinoma, whereby involvement of the serosa can lead to intraperitoneal seeding and spread (pseudomyxoma peritonei or mistaken for mucinous ovarian tumours – the abdomen fills with tenacious semisolid mucin)

Tumours of the appendix, Mucocele

______ • Houses the abdominal viscera and is lined by a single layer of mesothelial cells; these cover the visceral and parietal surfaces and are supported by a thin layer of connective tissue to form the ______

PERITONEAL CAVITY, peritoneum

PERITONEAL CAVITY:

• Sterile peritonitis • Infection • Sclerosing retroperitonitis • Tumours

PERITONEAL CAVITY • ______: Chemical irritation causing inflammation e.g. due to leakage of bile (e.g. from perforation of rupture of the biliary system) or pancreatic enzymes (e.g. in acute haemorrhagic pancreatitis). ______ can cause haemorrhage into the peritoneal cavity where it acts as an irritant. ______ introduced surgically also induces foreign body-type granulomas and fibrous scarring e.g. talc, sutures. ______ release keratins and also induce an intense granulomatous reaction

Sterile peritonitis, Endometriosis, Foreign material, Ruptured dermoid cysts

PERITONEAL CAVITY • ______: ______ occurs when bacteria (e.g. E.coli) from the GI lumen are released into the abdominal cavity, most commonly following perforation/damage to the bowel.

Infection, Bacterial peritonitis

PERITONEAL CAVITY • ______ (______): characterized by dense fibrosis that may extend to involve the mesentery. Many cases through to be related to IgG4-related sclerosing disease, an immune-inflammatory disorder that can lead to fibrosis in a wide variety of tissues

Sclerosing retroperitonitis, idiopathic retroperitoneal fibrosis

PERITONEAL CAVITY • ______: (Primary) ______ are malignant tumours arising from the peritoneal lining, similar to tumours of the pleura and pericardium. Peritoneal mesotheliomas are almost always associated with significant asbestos exposure.

Tumours, Mesotheliomas

GI PATHOLOGY Flashcards

(278 cards)