Luminal Infections and Disorders Flashcards

Question

What impact do C. Difficile toxins have on gut epithelial cells?

Answer 1

GTP binding proteins belong to the Rho family – cytoskeleton regulatory proteins Toxin drives glucosylation of GTPases (like Rho) causes the collpase of the actin cytoskeleton

Answer 2

C. Difficile mechanism of action - Cellular damage and immunopathology 1. B toxin is more important in physiopathology – lead glucosylation of GTPase – cell will die 2. Toxins can also pass through the tight junctions and interact with neutrophils which are then recruited driving a large immune response

Answer 3

Exudate of dead epithelial cells, fibrin and inflammatory cells – forms pseudo membrane

Answer 4

The most common cause of nosocomial (originating in hospitals) diarrhoea, with a severity spectrum ranging from asymptomatic carriage, mild to moderate diarrhoea, to life- threatening pseudomembranous colitis It has been steadily increasing from the 1980s to the 2010s, now endemic in healthcare institutions and in the community, but slightly decreasing

Answer 5

Clinical features * Asymptomatic carriage * Diarrhoea / simple colitis * Pseudomembranous colitis * Fulminant colitis Diagnosis * Clinical features * Stool analyses: Antigen (Toxin or Bacteria (enzyme)) * Culture Treated * Antibiotics - Metronidazole or vancomycin? Fidaxomicin - needs to be specific as killing normal microbiota could promote C. Difficle * “Faecal transplants” - Prevent bacteria from colonizing by replacing the microbiome back following antibiotics (prevention) * Immunotherapy - not much evidence Note - Probiotics not succesful

Answer 6

Very important! Infection control – removal of spores of C. difficile – hospital environment cleaning – spores resistant to alcohol – need to use bleach Antibiotic stewardship – avoid antibiotics that promote CD infections

Answer 7

Hypervirulent strains – tcdC gene deletion - negative regulator of toxin release – deletion leads to increase levels Resistant to quinolone antibiotics - not directly used to treat C. Difficile but when people were treated with quinolone C.Difficile was left behind whereas everything else was killed

Answer 8

H. Pylori Infection

Answer 9

Vibrio Cholerae

Answer 10

Clostridioides difficile

Answer 11

Gastro-enteritis = inflammation of the digestive tract, causing nausea, vomiting, abdominal pain, diarrhea, eventually fever. Can be upper or lower digestive tract Can be caused by: * Viral – quite common – stomach flu * Bacterial causes – main group – microbial food poisoning – two big types within this category – infection (viable microorganism was ingested) & intoxication (ingest the toxin but not the whole viable microorganism) * Parasite causes – less common in the western world – more common in the developing world

Answer 12

Infective - Campylobacter spp, Salmonella spp, shigella Both - E. Coli Toxic/intoxication - Clostridium perfringens, Bacillus cereus, Staphylococcus aureus Clostridium botulinum and Vibrio cholerae

Answer 13

Blood in diarrhea is dependent on the degree of tissue invasion - e.g. shigella and salmonella travel quite deep causing bleeding.

Answer 14

Endogenou pathogens in food - no cooked thoroughly Drinking water contaminated with feces Human to human - faecal contamination

Answer 15

The number of pathogens needed to cause disease in the new host Varies with the pathogen Relatively high for all bacteria whereas viruses require a lower load

Answer 16

Campylobacter species - Commonest cause of diarrhoea in the developed World * Infects both the small and large bowel * C. jejuni and C. coli * Mechanism - infective * Typically gives **bloody and fever** but can give bloody with no fever or watery with fever * Associated with poultry (grows well in the gut of chicken), wild birds and other animals and in their milk and water – zoonotic * Diagnosis - Clinical and stool culture * Treatment - Antibiotics * Complications - !! Guillain-Barré Syndrome!!

Answer 17

Non-typhi Salmonella spp - Major cause of foodborne disease world-wide (2nd after Campylobacter) * Small and large bowel * Infective mechanism * Very wide range of clinical manifestations - all four combinations of fever and diarrhea - Often serious: fever, diarrhoea, vomiting * Associated with poultry/eggs (Typhi: Only human reservoir) * Diagnosis - clinical symptoms and stool culture * Treatment - Antibiotics - Be careful due to MDR

Answer 18

Clostridium perfringens * Small bowel * Intoxication - toxin - Bacteria sporulate in small intestine and produce an enterotoxin - destruction of villus tips with resultant pain and diarrhoea * Symptoms - Watery no fever or Watery with fever - can also lead to myonecrosis (necrosis of the skin up to th muscle). * Associations - Warm food contamination with spores - bulk cooking of meat * Diagnosis – stool and detection of toxin * Treatment – supportive

Answer 19

Clostridium botulinum * Small bowel * Mechanism - Intoxication * Symptoms - Watery with no fever or watery with fever - can be absorbed into the blood stream resulting in neuro-Botulism (toxin mediated paralytic illness) + wound botulism – toxin on the skin – seen in heroin users * Associated - Widely distributed in nature - soils, lake sediments, vegetables, GI tract of mammals, birds and fish. Home-canned or fermented foods. * Diagnosis - Stool culture + Detection of toxin * Treatment - Supportive + (Anti-Toxin)

Answer 20

Staphylococcus aureus * Small bowel * Mechanism - intoxication - heat stable toxin * Symptoms - Very acute vomiting response often followed by diarrhoea - watery with or without fever * Source - Contaminates salted foods and dairy produce * Complication - sepsis * Diagnosis - Not necessary * Treatment - supportive

Answer 21

Bacillus cereus * Small bowel * Mechanism - Intoxicating - toxin * Symptoms - Acute vomit response followed by diarrhoea - watery with or without fever * Source - Spore germinate in warm cooked rice * Diagnosis - Not necessary * Treatment - supportive Cool Fact - Separate toxins for vomiting and diarrhoea responses! (ingestion of toxin directly for vomiting response)

Answer 22

Norovirus - Most common viral cause of epidemic gastroenteritis worldwide - Winter vomiting disease * Small bowel and large bowel? * Mechanism - infective and intoxication * Symptoms - Vomiting, diarrhoea, low grade fever - watery with or without fever * Source - Direct contact with fecal matter or vomit – direct contact but some outbreaks associated with shell-fish * Diagnosis - Clinical and PCR * Treatment - supportive

Answer 23

E. Coli – many different strains that result in different clinical manifestations - all the different types of diarrhea **Intoxication** - Enterotoxigenic E. Coli Three different **invasive types**: EPEC – **children** – small intestine EIEC – more like shigella EHEC – more severe manifestations (colon)

Answer 24

1. Food-borne (faecal contamination) 2. Faecal-oral transfer 3. Environmental contamination by domestic animals EHECs are highly infectious agents - Infectious dose c. 10 bacteria

Answer 25

1. Attachment to microvilli 2. Use type III secretion system which will inject the toxin into the cell 3. Results in the formation of its own gene – intimin 4. Results in micro-villi destruction and pedestal formation due to the formation of polymerized actin

Answer 26

E. Coli - Summer Salmonella - Summer Campylobacter - Spring Norovirus - Winter

Answer 27

GORD ( gastro-oesophageal reflux disease) These are different ways GORD can manifest: * Oesophagitis * Barrett’s oesophagus * Benign oesophageal stricture Oesophageal Motility disorders ( e.g. Achalasia) Eosinophilic oesophagitis Oesophageal cancer

Answer 28

Deglutition (swallowing( is performed by striated muscle 1. Bolus is formed 2. The upper oesophageal sphincter relaxes 3. Food enters the esophagus 4. Primary peristaltic wave is triggered all the way down 5. Lower oesophageal sphincter relaxes 6. Food enters into stomach

Answer 29

Allows us to track pressure changes in the oesophagus. High pressure areas shown in red and low pressure in green/blue

Answer 30

* Main symptoms is **dysphagia** – alarm symptom – manifestation of severe disease – inability/reduced ability to swallow * Often if there is inflammation, it is accompanied by odynophagia (pain on swallowing) * Heartburn – burn retrosternally – acid reflux into esophagus * Acid regurgitation – acid is felt and tasted * Waterbrash – characteristic symptom of increased saliva production due to the aforementioned symptoms * Dental erosions

Answer 31

Dysphagia - difficulty swallowing solids or liquids - alarm symptom – we want to exclude cancer Can be... 1. **Oropharyngeal** - difficult bringing the bolus from the mouth to the oesophagus - usually neurological cases - stroke 2. **Oesophageal**

Answer 32

**Elderly** – think neurological causes if intermittent/long standing or sinister esophageal cancer if new, progressive with regurgitation and weight loss Cancer – problems with solids first and then liquids – progressive dysphasia **Younger people** – can’t swallow – same difficulty with solid and liquids – think about dysmotility – number one is achalasia but can also be secondary to acid reflux **Young patients** – food bolus obstruction – think eosinophilic eosophagitis Extra... **Hoarse voice** – think of ENT causes (or advanced tumour left recurrent laryngeal nerve is infiltrated/impacted by advanced oesophageal cancer) **Pharyngeal pouch** (posterior to the larynx) – pouch that accumulates and prevents food movement – think of this when people get regurgitation of food from previous days

Answer 33

Investigations * **Endoscopy and biopsy** - gold standard * **Barium swallow** – swallowing a barium meal – gives us a more dynamic information about the way esophagus contracts – can’t tell us about inflammation or potential cancers * **Oesophageal function test** – manometry (measure pressure), pH (reflux) and impudence monitoring (looking for material refluxing that isn’t acidic) – look at motility and look at the exposure of acid

Answer 34

1. **Transient lower oesophageal relaxations** (sphincter becomes relaxed) – daytime reflux, small or no HH and often no esophagitis (no inflammation of the lining) – more common 2. **Reflux with low lower esophageal sphincter pressures** – less common, nocturnal reflux – associate with the hiatus hernia (hernia slides up and down) – disrupts the lower esophageal sphincter function – causes esophagitis and much more likely to suffer Barret’s Other mechanisms also potentially involved... * Increased acid production by the stomach

Answer 35

TYPICAL symptoms of GORD * Heartburn – behind the sternum * Acid regurgitation * Waterbrash – excessive salivation Precipitating factors - after a meal and postural (bending over, at night)

Answer 36

* Lifestyle measures – smoking, alcohol, diet (staying away from triggers - caffeine, high fat, carbonated drinks, etc. ) weight reduction * Mechanical – posture, prevent lifting heavy weights, elevate head in bed * Antacids are commonly used * Acid suppression - Proton-pump inhibitors or H2 antagonists * Complex GORD – particularly in young people – surgical operation – reconstruct the lower Oesophageal sphincter

Answer 37

Complications of GORD * Oesophagitis * Oesophageal Stricture – narrowing of the esophagus in response to continuous inflammation * Barret’s Oessophagus * Adenocarcinoma (Most arise from Barrets)

Answer 38

OESOPHAGEAL STRICTURE= narrowing of Gullet Benign * GORD up to 10% - most common cause * Barrett’s * Extrinsic compression – tumours in the mediastinum or lung * Post-radiotherapy Malignant * Oesophageal cancer

Answer 39

Treatment 1. PPI – omeprazole 2. Dilate the narrowed oesophagus - Dilatation – opening up – stretch – push dilators - CRE balloons or push dilators

Answer 40

Barret’s esophagus – growth of a stomach like epithelium up into the esophagus – **gastric columnar epithelium growing into the esophagus** (squamous epithelium replaced) – esophagus is made more robust Problematic – prone to develop of dysplastic changes – adenocarcinoma – premalignant condition - increased risk. Commonest in obese men >50 Often asymptomatic – symptoms of Acid reflux

Answer 41

1. Ablation – stop the development of barrets – burn the area - especially if there is a high risk fo cancer. 2. Long term treatment people with proton pump inhibitors

Answer 42

Two cancer types 1. Adenocarcinoma is becoming more common – more in younger (average age still 60) - found in the lower third of the esophagus – more associated with obesity and Barret's. 2. Squamous cell -– mid/upper eosophagus – more in the older population - associated with smoking and alcohol – becoming less common

Answer 43

Gold standard - Upper endoscopy + biopsies used for diagnosis TMN Staging... * CT - metastases and lymph nodes * Endoscopic ultrasound – used to stage the tumour – depth of invasion of the tumour

Answer 44

Oesophageal cancer – 2/3 of cases there isn’t much we can do about it Palliation measures – relieve the difficulty swallowing – leads to ill-health due to malnutrition Entermetal sheet/stent opening the esophagus – improves quality of life but doesn’t change the prognosis

Answer 45

Normally... normal upper GI endoscopy Perform a barium swallow - dilated oesophagus with accumulation of barium above sphincter (hypertonic/tight sphincter) with trickle into the stomach Futher tests - Manometry which is used to confirm the diagnosis

Answer 46

Achalasia is a motility disorder Definition of achalasia – failure of the LOS to relax and absence of peristalsis – resulting in food staying in the esophagus. Dysphagia to liquid and solid with weight loss and chest pain. More common in young Endoscopic appearance is normal Complications – food and liquid back log into wind pipe – causing respiratory complications/infections

Answer 47

Best way to treat is to stretch the LOS (Endoscopic pneumatic dilatation) – Can cause acid reflux but relieves swallowing problems Other options - Surgical myotomy - Weaken the sphincter muscle - Botox injection – need multiple – not long lasting - POEM – non-invasive way to perform a myotomy

Answer 48

Eosinophilic esophagitis is an allergic condition that happens in the esophagus - asthma of the esophagus The esophagus becomes inflamed and does not contract properly. There is a build up of eosinophiles in the oesophagus.

Answer 49

* Presents in children and young adults * Presents as dysphagia or food bolus obstruction, regurgitation * Associated with atopy * More common in males – 3:1 * Can see endoscopic signs - furrows, rings and strictures

Answer 50

Diagnosis with biopsy Take 6 biopsies – 3 from the lower esophagus and 3 from the upper esophagus – 15 eosinophils per 15 powered field

Answer 51

1. **Topical steroid** – Budesonide (Jorvesa) or flucticasone dry powder inhaler – wipes out eosinophiles – first line 2. Children – elimination diet – dairy, eggs, nuts, soya, shellfish and wheat 3. PPI therapy 4. Sometimes get strictures – narrowing – these need to be dilated

Answer 52

Proton pump inhibitors - block H+/K+ ATPase in parietal cells from pumping out protons * PPI are unstable in acidic environments so they are enteric coated * Ingested in an inactive form and become trapped and activated by the acidic pH inside parietal cells * This is where they irreversibly bind to proton pumps (H+/K+ ATPase) – preventing them from pumping protons and new pumps take 24hr to synthesize (do not work via receptors) * But we get rebound hypersecretion upon PPI cessation H2 Antagonists * H2 antagonists bind to histamine type 2 receptors on the basolateral (antiluminal) surface of gastric parietal cells, interfering with pathways of gastric acid production and secretion

Answer 53

NICE recommends all patients taking NSAID or COX-2i should be given a PPI. Effective prevention of NSAIDs ulcers and complications

Answer 54

Iron deficiency - simply supplement with more iron.

Answer 55

Probably upper GI pathology with chronic blood loss! **Peptic ulcer** ( gastric or duodenal) In view of age gastric cancer needs excluding.

Answer 56

Upper GI endoscopy

Answer 57

H. Pylori – cause of peptic ulcer disease – resides in the gastric pits H. Pylori disrupts the epithelium – leading to ulcer formation H. Pylori - Has the ability to live along the epithelium of the stomach – produces bicarbonate and ammonia – buffers the acidic microenvironment

Answer 58

Testing for H. Pylori - Number one cause of peptic ulcer disease **Non-invasive** * Make a diagnosis H. Pylori using a breath test – administer radiolabelled urea (C-13) – urea is split by H. Pylori into bicarbonate – this can then be picked up in the breath as radiolabelled CO2 * Antibody measurement * Stool Antigen test – primary care **Invasive** * Culture – not commonly done – only used to determine antibiotic sensitivities * Histology * CLO test - Take a biopsy – place onto CLOtest kit – immediately see whether H. Pylori is present as it will cause a pH change

Answer 59

Aspirin/NSAIDs increase risks of ulcers and bleeding in HP-positive patients Test for and eradicate if positive Note - HP can also be linked to... * unexplained iron deficiency anaemia * Immune thrombocytopenic purpura - I.T.P * vitamin B12 deficiency Consider eradication therapy if positive

Answer 60

Triple therapy! 1x PPI and 2x Antibiotic Eradication confirmed using breath test or stool antigen test

Answer 61

Bulk of the pathology occurring in the GI tract is mucosal-based 1. **GI tract secretions** – acid, pepsin , biliary and pancreatic secretions can all injure the muscosa 2. The mucosa of the GI tract is sensitive to **ischaemia** – blood supply from outside in, so luminal aspect most at risk – this combined with high metabolic injury – makes it sensitive to ischaemia 3. Many **drugs** damaging to GI tract (as shown above) – NSAIDs, antibiotics, steroids and chemotherapy agents 4. **Immunological causes** – coeliacs disease 5. **Infections** - . Helicobacter, Salmonella, Shigella, E. coli, C. difficile, CMV 6. Radiation 7. Trauma - endoscopic procedures 8. Idiopathic - Ulcerative colitis and Crohn’s disease

Answer 62

* **Inflammation** * **Apoptosis or necrosis** - Apoptosis a useful diagnostic feature as not many conditions associated with this – suggests HIV, GVHD (graft versus host disease) and reaction to some drugs e.g. mycophenolate * **Erosion and ulceration** * **Hypoplasia and atrophy** * **Hyperplasia** * **Metaplasia** * **Dysplasia +/- neoplasia**

Answer 63

Gastritis is inflammation in your stomach lining Can be acute or chronic

Answer 64

Acute gastritis * Acute erosive / haemorrhagic gastritis - Ingestion of irritant chemicals * Acute H. pylori infection - Usually no or minor symptoms, so seldom seen in biopsies

Answer 65

Chronic Gastritis **Non-atrophic gastritis** – associated with chronic H. Pylori Infection **Atrophic gastritis** – associated with autoimmune gastritis (antibodies generated against the parietal cells – can be detect in blood – serology diagnostic) and chronic H. Pylori infection. Atrophic gastritis characterised by loss of parietal (acid secreting) and peptic (pepsin secreting) cells in gastric body. Extra... Loss of intrinsic factor secretion also possible leading to low vitamin B12 absorption – can lead to megaloblastic anaemia Intestinal type metaplasia and neuroendocrine cell hyperplasia are common features in atrophic gastritis

Answer 66

A hypersensitivity reaction to glutamine-rich proteins in wheat, barley and rye (gliadins, hordeins and secalins) - gluten Inflammation in the small intestinal mucosa impairs the absorption of nutrients Strong link to HLA haplotypes – class 2 – MHC on antigen presenting cells

Answer 67

Requires... 1. Histological changes of the duodenum 2. Detection of auto-antibodies 3. Response to gluten free diet Often picked up in asymptomatic individuals in iron deficiency anemia – malabsorption

Answer 68

Autoimmune diseases often go hand-in-hand Not unusual to diagnose dermatitis herpetiformis first followed by coeliac disease diagnosis

Answer 69

Histological features * Variable villous atrophy * Chronic inflammation in lamina propria * Increased CD8+ T-lymphocytes in epithelium * Epithelial damage * Crypt hyperplasia

Answer 70

Bacteria * Some bacterial infections – bacterial species are visible in biopsy - H. Pylori and Mycobacterium * Some produce a characteristic pattern of injury – pseudomembranous colitis in C. Difficile and neutrophil rich granuloma in Yersinia enterocolitica Viral infection * Infected cells can contain inclusion bodies – HSV and CMV can be diagnosed on a biopsy Fungal, Parasitic and Helminths * Fungal, protozoal and helminths are large enough to be seen in biopsies * Candida can be seen in esophageal biopsies

Answer 71

Organism responsible – C. Difficile - cause volcano lesions

Answer 72

IBD - refers to Ulcerative colitis and Crohn's disease Causes not fully understood 1. Loss of tolerance to normal commensal bacteria 2. Familial and genetic component – involved in immune pathways such as bacterial recognition 3. Environmental – food antigens and smoking (makes Crohn's worse but protective for UC) 4. Infection – no single organism identified

Answer 73

Biopsies in IBD 1. Allows one to make an initial diagnosis 2. Exclude other aetiologies 3. Distinguish between Crohn's and UC 4. Reponse to treatment 5. Complications/any other pathology Biopsies ideally taken from multiple sites

Answer 74

* Show Chronic relapsing and remitting course * Presentation is normally rectal bleeding * Incidence in peaks at 15-25 y/o and later peak between 60-70 * Confined to the mucosa * Involve rectum +/- left colon * Mainly limited to the large intestine and rectum * Continious inflammation * Whole colon in a continious distribution - pancolitis

Answer 75

Histology * Erythema * Ulceration * Granular appearance * Flat - loss of mucosal folds * Inflammatory polyps and pseudopolyps (arise from ulceration) * Chronic architectural changes

Answer 76

Commonly – rectum and left colon length Most severe cases – involvement of entire colon and rectum

Answer 77

Chronic, multifocal, relapsing condition that can affect any part of the GI tract Peak incidence 20-30 years with smaller peak 60-70 years. No gender difference Variety of presentations depending on part of GI tract involved e.g. abdominal pain, diarrhoea, weight loss, strictures and obstruction, fistulae Transmural inflammation (affecting all parts of the GI wall) that is often patchy and discontinuous (“skip lesions”)

Answer 78

Most common – small intestine, colon and anus whereas upper GI is less common

Answer 79

One of the most useful features – granulomas – aggregates of activated macrophages – 70% of cases Most common in the earlier stages of the disease – can be seen in the GI tract and draining lymph nodes

Answer 80

1. Aphthous ulcers in Crohn’s Disease - mouth 2. Ulceration extending into the anal canal and perianal skin 3. Discontinuous patchy nature of inflammation - skip lesions 4. Deep knife like fissuring ulcers (UC - flat bottomed ulcers) 5. Stricture formation - healing response narrows gut tube 6. Fistula formation - connection between two structures. 7. Granulomas 8. Transmural inflammation 9. More severe - cobblestone mucosa

Answer 81

Intestinal obstruction (stricture), fistulae and malabsorption (small bowel involvement) are typically only seen in Crohn’s disease Note: * Toxic dilatation – emergency – dilates and wall becomes thin and perforates easily * Amyloidosis – protein plaque formation

Answer 82

Risk increased in both UC and CD (highest in UC) Most commonly colorectal carcinomas but also increased risk of small bowel carcinomas and other malignancies e.g. bile duct carcinomas, leukaemias

Answer 83

* Infective colitis – mimic CD * Ischaemic colitis – any part in large bowel – more common in splenic flexure – histology helps to distinguish * Diverticular disease – can result in fistulas * Drug-induced colitis – ileocolic inflammation with NSAIDs * Radiation colitis * Neoplasia

Answer 84

* Crohn’s disease * Ischaemic colitis * Diverticular disease * Diaphragm disease – NSAIDs * Neoplasia

Answer 85

Microscopic colitis - Normal appearance of colonic and rectal mucosa at endoscopy but increased in chronic inflammatory cells in lamina propria - affects the large bowel Two types * Collagenous colitis * Lymphocytic colitis Presentaiton * Typically in older patients * Watery diarrhea over several months – need biopsy for diagnosis Causes * Often not identified * Lymphocytic colitis associated with coeliac * Drugs - lansoprazole and NSAIDs Treatment * steroids (budesonide)

Answer 86

qFit - immunochemical test for small quantities of blood If qFit positive - patients sent for a colonoscopy

Answer 87

Looking for polyps – can be raised or flat – some of these may turn into colorectal cancer if not treated

Answer 88

* Polypoid lesion on a stalk (can also be flat), projecting into the lumen of the colon * Smooth surface * Well circumscribed * No obvious ulceration or haemorrhage

Answer 89

The patient should be staged with CT scan or MRI scan - TMN staging

Answer 90

1. **Adenomatous polyps** – highest progression to malignancy (adenocarcinoma) 2. **Hyperplastic metaplastic polyps** - don't have malignant potential * Third - classified as hyperplastic but has a serrated polyp – problem is that they are often flat making them hard to recognise So no, not all colonic polyps progress to adenocarcinoma

Answer 91

The adenoma-carcinoma sequence refers to a stepwise pattern of mutational activation of oncogenes (e.g. K-ras) and inactivation of tumour suppressor genes (e.g. p53) that results in cancer. APC – tumour suppressor – negative regulator of cell division/growth – once this genes is deleted, we see a higher predisposition of cancer

Answer 92

Commonest cause of iron deficiency anaemia is blood loss Commonest cause of blood loss is GI bleeding

Answer 93

* **Rectal bleeding** – exclude colorectal cancer especially in older patients * **Weight loss** – is a late presentation – not a good sign * Anaemia/thrombocytosis * **Alteration in the bowel habit** – vast majority of cases is persistent diarrhoea – more common in the cancers of the right-side bowel (ascending colon) * Frequent diarrhoea is the middle of the night – indicates an organic problem rather than functional * **New Onset over 50 years** * **Family history of bowel cancer** * Past medical history of IBD

Answer 94

Haemorrhoids Colon polyps Colon Cancer Inflammatory bowel disease

Answer 95

GRADE of the cancer – depends on the pattern of cancers cells under the microscope – higher grade = more aggressive Stage – standard way to sum up how far the cancer is spread

Answer 96

TNM staging system * **T** refers to how far the primary tumor has grown into the wall of the GI tract and into nearby organs. * **N** refers to cancer spread to nearby lymph nodes. * **M** indicates whether the cancer has metastasized (spread to distant organs).

Answer 97

Liver (most common for colorectal cancer), Lungs and Brain – main sites of metasteses

Answer 98

* T1- mucosa and submucosa * T2 – Muscularis propria * T3 - Serosa * T4 (associated with metastatic disease) – spread to nearby structures past the serosa – in the peritoneum and vasculature (bad news) Note * T1-T3 – contained within the lining of the organ * In T3 tumours – you still can get positive lymph nodes as cells may end up there

Answer 99

1. Surgery - common 2. Chemotherapy 3. Radiotherapy

Answer 100

1. **Diet high in red meats and processed meats** raises colorectal cancer risk. 2. Cooking meats at very high temperatures (frying, broiling, or grilling) creates chemicals that might raise cancer risk. 3. Diet low in fibre 4. Obesity 5. Physical inactivity. 6. Smoking 7. Alcohol excess. 8. A family history of colorectal polyps or colorectal cancer. 9. History of inflammatory bowel disease. 10./ Older age

Answer 101

1. **Recto-sigmoid area** – account for 1/3 – most common 2. Right side of the colon – account for 20/30%

Answer 102

* Population over the age of 50 routinely and regularly checked for occult blood (qFIT) * If positive they get a colonoscopy Aim – prevent spread, screen and act early - improved outcomes

Answer 103

Yes! * Third commonest cancer in Scotland * Colorectal is the second most common cause of cancer morality

Answer 104

Hyperplasia - Tissue growth to an **increase in cell number** (increase in cell size = hypertrophy) Can be physiological or pathological

Answer 105

Metaplasia - A change from one fully differentiated cell type to another fully differentiated cell type

Answer 106

Descriptive term used by pathologists to indicate a pattern of **disordered growth, architecture and maturation within a tissue** (usually epithelial in nature) Unlike metaplasia and neoplasia, it does not describe a pathological process, rather an appearance seen down the microscope Important to recognise as it reflects underlying abnormalities in the regulation of cell growth and differentiation - may show pre-neoplastic or neoplastic changes (note dysplasia can also revert back to normal)

Answer 107

The development of a neoplasm, i.e. an abnormal mass of tissue, the **growth of which exceeds and is uncoordinated with that of normal tissue**, and which persists even after the evoking stimulus (if known) is removed Neoplasms may be benign or malignant

Answer 108

Dysplasia is commonly divided into low grade and high grade based on the extent by which the growth pattern deviates from that of normal tissue

Answer 109

In epithelial tissues, severe dysplasia is often referred to as carcinoma in situ (also known as intraepithelial neoplasia)

Answer 110

1. Hyperchromatism - Dark staining of nuclei reflecting an increase in DNA content, e.g. polyploidy 2. Nuclear pleomorphism - Variation in nuclear shape (and size) 3. Loss of orientation - Many normal epithelial cells show “polarity” 4. Cell crowding and stratification - Reflects a loss of normal contact inhibition 5. Increased and/or abnormal mitotic figures Reflects increased cell proliferation

Answer 111

Adenocarcinoma - Adenocarcinomas start in glandular cells called adenomatous cells. Glandular cells produce mucus/fluids to keep tissues moist. Squamous cells carcinoma - starts in squamous cells. These are the flat, surface covering cells found in areas such as the skin or the lining of the throat or food pipe (oesophagus).

Answer 112

* Chemical carcinogens * Physical agents * Infections * Inherited susceptibility * Hormonal stimulation

Answer 113

* Direct or indirect damage to DNA * Reduced ability to repair DNA damage * Increased stimuli to proliferate * Reduced ability to inhibit growth * Defects in apoptosis

Answer 114

* Lymphatic * Vascular * Perineural and intraneural * Spread across cavities * Iatrogenic

Answer 115

Not unproblematic - can have serious clinical consequences * Bleeding – erosion and ulceration * Space occupying lesions within skull * Compression of adjacent structures - Obstruction of lumina - e.g. intussusception in GI tract * Hormonal effects a) increased production b) decreased production

Answer 116

Telescoping effect due to the presence of a polyp in the small and large bowel – compresses the veins and arteries in that area causing ischemia

Answer 117

It can be difficult to predict the behaviour of some neoplasms (tumours) These are often referred to as tumours of uncertain (or borderline) malignant potential.

Answer 118

Tumours fall into 2 main categories: 1. Show extensive local invasion but almost never metastasize – prone to local recurrence if incompletely excised 2. Tumours that appear benign which can develop distant metastases – often presenting many years after initial diagnosis

Answer 119

An attempt to predict the aggressiveness of a cancer based on its microscopic features * High grade cancers are typically poorly differentiated and tend to have a worse prognosis * Low grade cancers are well differentiated and tend to have a better prognosis

Answer 120

* Tiredness (anaemia) * Bleeding * Anorexia and vomiting * Weight loss * Pain caused by obstruction * Dysphagia * Alteration in bowel habit (colorectal)

Answer 121

1. Squamous Cell Carcinoma - 90% of oesophageal cancers worldwide with 80% of cases occur in developing countries 2. Adenocarcinoma - Commonest type in the UK

Answer 122

Risk factors include * **Tobacco and alcohol** * Diet * Infection - ?Fungal oesophagitis (Candida) Evidence for the role of human papillomavirus (HPV) is lacking * Genetic factors

Answer 123

Most associated with acid reflux and barrett’s esophagus (Squamous epithelium to columnar epithelium) Risk factors – obesity and male sex

Answer 124

Tumour STAGE is the most important prognostic factor for both squamous cell carcinomas and adenocarcinomas Good prognosis for tumours confined to the mucosa Many tumours picked up late 10-20% survival for adenocarcinomas involving deep muscularis propria

Answer 125

* Incidence increases with age * Males > females * Familial link in about 10% * Small percentage have germline mutations e.g. TP53, CDH1 genes Often presents late Aetiology multifactorial: diet, H. pylori, bile reflux - chronic gastritis is a common theme Tumour can grow quite large until symptoms are caused – stomach can accommodate size - reason why it is picked up late

Answer 126

**Intestinal** * The majority of cases in high incidence areas - Japan, east Asia, eastern Europe and parts of S America * Increased risk in patients with FAP (Familial adenomatous polyposis) **Diffuse** * Relatively more common in low incidence areas * Often younger patients * Female > male * Mutation or inactivation of CDH1 gene a common feature

Answer 127

Gastric polyps are intraluminal projections of mucosal or submucosal tissue. They are generally asymptomatic. While these lesions are typically benign, they do have the potential of containing local dysplasia and progression to invasive cancer.

Answer 128

Uncommon * **Adenocarcinoma** * **Neuroendocrine tumours** * **Gastrointestinal stromal tumor** (GIST) * **Lymphoma** - Enteropathy type T-cell lymphoma (EATL) in coeliac disease

Answer 129

Epithelial tumours associated with the synthesis of hormone or neurotransmitter-like substances. Can be difficult to predict their behaviour Risk depends on… **size** (bigger – more aggressive), **site** (appendix – less aggressive / small intestine – more aggressive), **grade** (1-3 – based on proliferative activity)

Answer 130

GISTs - Soft tissue tumour that can arise anywhere in the GI tract - Borderline tumour type * Related to “pacemaker” cells in the muscularis propria * Malignant tumours are a type of sarcoma * High proportion have activating mutaiton in the KIT receptor tyrosine kinase gene * Stomach is the commonest site

Answer 131

Colonic polyps are common - **Inflammatory** - IBD, lymphoid - **Hamartomatous** – contain normal components of the Gi tract but in an abnormal proportion or arranged differently - e.g. Juvenile polyps, polyposis and Peutz-Jegher syndrome - **Hyperplastic** - **Lesions** in the submucosa presenting as a “polyp”

Answer 132

**Adenomas** - benign * Tubular * Tubulovillous * Villous **Adenocarcinomas** - malignant

Answer 133

* Peak incidence 60-79 * No gender difference with exception of rectal cancers (M>F) * 55% of tumours rectum/sigmoid * 22% of tumours caecum/ascending colon Most sporadic - no family history About 5% are associated with a known familial syndrome (FAP, HNPCC) or IBD

Answer 134

* Excessive calories relative to requirement * Low fibre * High intake of refined carbohydrates * High intake of red meat * Low intake of protective micronutrients e.g. vitamins A, C, D and E

Answer 135

Other risk factors: * First degree relative with Colorectal cancer * Inherited syndromes (FAP, HNPCC etc.) * Alcohol in rectal carcinomas * Smoking * Inflammatory bowel disease * Occupational factors e.g. solvents * Radiation

Answer 136

**Inactivation of APC** (Adenomatous Polyposis Coli) tumour suppressor gene seen in about 80% of colorectal carcinomas Mutation is typically an early event in the transition from adenoma to carcinoma

Answer 137

1. **Microsatellite instability pathway** – inactivation of DNA mismatch repair genes – increase the mutation rate – not associated with the typical adenoma-carcinoma sequence - more common in right colon 2. **“Serrated neoplasia” pathway** - typically have a mutation in either BRAF or KRAS proto-oncogenes - More common in the right colon

Answer 138

FAP - About 1% of colorectal carcinomas are associated with FAP HNPCC - Up to 5% associated with Hereditary nonpolyposis colorectal cancer (lynch syndrome) Of sporadic carcinomas, ≥30% may be associated with an inherited defect

Answer 139

Bowel screening – ages 50-74 – uses qFit test with referral to colonoscopy if positive result

Answer 140

Ulcerative Colitis Pathology * Always starts from the rectum * Continuous manner - Inflammation spreads to various areas of the colon * Passed the splenic flexure = pan-colitis (important implications in terms of outcome – more parts of the colon affecting – longer term prognosis is worse) * Mucosal inflammation (lining of the wall) Presentation * Rectal bleeding - mucosal inflammation starting from the rectum – leads to rectal bleeding) * Diarrhea (due to irritation of lining) * Left lower abdominal pain * Young patients with rectal bleeding, diarrhea – we think UC (perform colonoscopy)

Answer 141

Crohn’s Disease Pathology * Starts at the ileocecal junction * Can spread to any part of the GI system -Many instances it doesn’t affect the rectum * Discontinuous inflammation (skip lesions) * Trans-mural inflammation * Possibility of creating an abscess, perforation and fistula formation (usually in the rectum) * Formation of strictures (inflammation and replacement of tissue by fibrous tissue) Presentation * Only show rectal bleeding when there is inflammation in rectal region * Different diarrhea - small bowel affected – increased motility but also because of malabsorption * Crohns leads to malabsorption - B12, folate, iron, etc * Lower right abdominal pain

Answer 142

Microscopic colitis – **profound diarrhea but no other classical signs of IBD** Taking biopsy you see lymphocytes and fibrous deposition Associated with taking medication (PPIs) – responds to classical treatments

Answer 143

When severe, toxic megacolon (dilation) may occur Dilation caused by significant inflammation that impacts the bowel's ability to contract

Answer 144

* Diffuse abnormality of the mucosal surface of the colon - inflammation * Pseudopolyps present between areas of ulceration

Answer 145

* Pseudopolyp with adjacent mucosal ulceration - mucosal ulceration create polyps * Ulceration - break in the mucus membrane * Crypt abscess formation - inflammatory cells build up * Granulation tissue - healing response * Inflammation confined to the mucosa/submucosa

Answer 146

* Thickening of the bowel wall * ‘Cobblestone’ appearance of the small bowel mucosa * May see ‘fat wrapping’ - movement of fat into the intestinal wall

Answer 147

* Fissuring ulceration (deep-knife like) with purulent exudate (white blood cell accumulation) * Accompanying chronic inflammation and fibrosis - causing strictures * Granulomata (non-caseating) with giant cells * Lymphoid follicles also present

Answer 148

Blue areas – Dysplastic glands forming tubular and villous structures – adenoma Red area - Abnormal glands invading the wall of the colon with a stromal reaction – adenocarcinoma - more abnormal looking

Answer 149

* Numerous nodules of variable size * Nodules present throughout the whole liver * Yellow colour implies the presence of fat * May be large (earlier) or small (late stage)

Answer 150

* Nodular architecture affecting the whole slide with disruption of normal lobular relationships * Nodules of hepatocytes separated by bands of fibrous tissue (shown on image) * Bridging fibrosis between nodules – from one portal triad to another * Mild inflammation, particularly within fibrous bands

Luminal Infections and Disorders Flashcards

(189 cards)