GIT

Question 1

H Pylori

Answer 1

• The most common cause of chronic gastritis
• Typically affects antrum → increased gastric acid production. In later disease can affect the body and progress to pangastritis
• H pylori gastritis induced mucosal associated lymphoid tissue (MALT) → MALToma (B cell lymphoma)
• Intestinal metaplasia develops in chronic gastritis (all causes) and is a risk factor for gastric adenocarcinoma
• Both intestinal and diffuse types of gastric adenocarcinoma are associated with H. pylori.

Question 2

Autoimmune gastritis

Answer 2

• 10% of cases of chronic gastritis
• Autoimmune gastritis is associated with loss of parietal cells, which are responsible for secretion of gastric acid and intrinsic factor.
• Leads to pernicious anaemia (lack of intrinsic factor → can’t absorb B12 at terminal ilium)
• The absence of acid production stimulates gastrin release, resulting in hypergastrinemia and hyperplasia of antral gastrin-producing G cells.
• Characterised by sparing of antrum, with otherwise diffuse mucosal damage of the oxyntic (acid producing) mucosa within the body and fundus → REDUCED acid production
• Diffuse mucosal damage causes atrophy and loss of rugal folds
• Leads to pernicious anaemia
• Increased gastrin production, reduced gastric acid
• Associated with acholrhydria (compared with H pylori which ma have normal or hypochlorhydria)

Question 3

Carcinoid tumours:

Answer 3

• Carcinoid tumors arise from the diffuse components of the endocrine system and are now properly referred to as well-differentiated neuroendocrine tumors.
• The term carcinoid (carcinoma-like) was applied because these tumors tend to have a more indolent clinical course than GI carcinomas.
• Most are found in the GI tract, and more than 40% occur in the small intestine
• The tracheobronchial tree and lungs are the next most commonly involved sites.
• associated with endocrine cell hyperplasia, autoimmune chronic atrophic gastritis, MEN-I, and Zollinger-Ellison syndrome.
• Symptoms are determined by the hormones produced.
• tumors that produce gastrin may cause Zollinger-Ellison syndrome,
• ileal tumors may cause carcinoid syndrome, which is characterized by cutaneous flushing, sweating, bronchospasm, colicky abdominal pain, diarrhea, and right-sided cardiac valvular fibrosis.
• Carcinoid syndrome occurs in fewer than 10% of patients and is caused by vasoactive substances secreted by the tumor into the systemic circulation.
• When tumors are confined to the intestine, the vasoactive substances released are metabolized to inactive forms by the liver, a “first-pass” effect. This can be overcome by a large tumor burden or, more commonly, when tumors secrete hormones into a nonportal venous circulation. Therefore strongly associated with metastatic disease in the liver since the bioactive products can be released directly into systemic circulation
• The most important prognostic factor for GI carcinoid tumors is location.
• Foregut carcinoid tumors, those found within the stomach, duodenum proximal to the ligament of Treitz rarely metastasize and are generally cured by resection. This is particularly true for gastric carcinoid tumors that arise in association with atrophic gastritis
• Midgut carcinoid tumors that arise in the jejunum and ileum are often multiple and tend to be aggressive.
• Hindgut carcinoids arising in the appendix and colorectum are typically discovered incidentally. Almost always benign.
• Rectal carcinoid tumors tend to produce polypeptide hormones and, when symptomatic, present with abdominal pain and weight loss. Because they are usually discovered when small, metastasis of rectal carcinoid tumors is uncommon.

Question 4

Gastrointestinal Stromal TUmour (GIST):

Answer 4

• GIST is the most common mesenchymal tumor of the abdomen, occurs most often in the stomach (>50%), and is related to benign pacemaker cells, (interstitial cells of Cajal) of the gastrointestinal muscularis propria.
• Tumors generally have activating mutations in either KIT or PDGFRA tyrosine kinases and respond to specific kinase inhibitors → TKI imatinib
• Usually adults ~60, <10% are in children and GISTs in children may be related to Carney triad (nonhereditary syndrome of unknown etiology seen primarily in young females that includes gastric GIST, paraganglioma, and pulmonary chondroma)
• gastric GISTs less aggressive than those arising in the small intestine.
• Morphology
• Primary gastric GISTs can be quite large, as much as 30 cm in diameter
• They usually form a solitary, well-circumscribed, solid mass. Can ulcerate, sometimes bleed
• Can project outward toward the serosa
• Recurrence or metastasis is rare for gastric GISTs smaller than 5 cm but common for mitotically active tumors larger than 10 cm

Question 5

Ischaemic bowel disease:

Answer 5

• Acute or chronic
• Damage can range from mucosal infarction, extending no deeper than the muscularis
• mucosae; to mural infarction of mucosa and submucosa; to transmural infarction involving all three wall layers.
• While mucosal or mural infarctions can follow acute or chronic hypoperfusion, transmural infarction is typically caused by acute vascular obstruction.
• watershed zones include the splenic flexure, where the superior and inferior mesenteric arterial circulations terminate, and, to a lesser extent, the sigmoid colon and rectum where inferior mesenteric, pudendal, and iliac arterial circulations end

Question 6

Coeliac disease:

Answer 6

• Reaction to gliadin in gluten
• Associated HLA p-DQ2 and HLA-DQ8 proteins
• malabsorptive diarrhea in celiac disease is due to loss of brush border surface area, including villous atrophy
• Individuals with celiac disease have a higher than normal rate of malignancy.
• The most common celiac disease-associated cancer is enteropathy-associated T-cell lymphoma (EATL), an aggressive lymphoma of intraepithelial T lymphocytes.
• Small intestinal adenocarcinoma is also more frequent in individuals with celiac disease. Thus, when symptoms such as abdominal pain, diarrhea, and weight loss develop despite a strict gluten-free diet, cancer or refractory sprue, in which the response to a gluten-free diet is lost, must be considered

Question 7

Whipples disease:

Answer 7

• Bacterial enterocolitis in genetically susceptible (caucasian men) pts caused by gram-positive actinomycete, named Tropheryma whippelii
• organism-laden macrophages accumulate within the small intestinal lamina propria and mesenteric lymph nodes, causing lymphatic obstruction
• The clinical presentation of Whipple disease is usually a triad of diarrhea, weight loss, and arthralgia. Extraintestinal sx can exist for month/yrs before intestinal sx

Question 8

Tumours of anal canal

Answer 8

• The anal canal can be divided into thirds.
• The upper zone is lined by columnar rectal epithelium;
• the middle third by transitional epithelium;
• and the lower third by stratified squamous epithelium.
• Carcinomas of the anal canal may have typical glandular or squamous patterns of differentiation, recapitulating the normal epithelium of the upper and lower thirds, respectively
• Pure squamous cell carcinoma of the anal canal is frequently associated with HPV infection, which also causes precursor lesions such as condyloma acuminatum

Question 9

Appendiceal tumours:

Answer 9

• The most common tumor of the appendix is the well differentiated neuroendocrine (carcinoid) tumor.
• This neoplasm, which is almost always benign, most frequently forms a solid bulbous swelling at the distal tip of the appendix, where it can reach 2 to 3 cm in diameter.