Histopathology 1 - Upper and Lower GI, Pancreas, Gall Bladder and Liver Flashcards
Define metaplasia
Reversible change in one mature and functional cell type for another mature and functional cell type
Example of Metaplasia
Barrett’s Oesophagus
What can Barrett’s progress to? Via what pathway?
Adenocarcinoma of the Oesophagus via the Metaplasia - dysplasia pathway
What are the two main pathways of GI Cancer?
Example of each
Metaplasia-dysplasia pathway
(Barrett’s –> Adenocarcinoma of the Oesophagus)
Adeno-carcinoma pathway
(Colorectal Cancer: benign polyps –> adenocarcinoma)
4 defining features of a cancer
Gland formation
Mucin Screening
Make Keratin (even in non-keratinised tissues)
Inter-celllular bridges
Two types of Cancer in GI
Adenocarcinoma
Squamous Cell Carcinoma
How to distinguish adenocarcinoma and squamous cell carcinoma?
Adenocarcinoma is gland forming and/or mucin secreting
Squamous Cell Carcinoma
Make Keratin (even in non-keratinised tissues)
have Inter-celllular bridges
Cancer cell producing Inter-cellular bridges. What is the type of cancer?
Squamous Cell Carcinoma
Cancer cell secreting mucin. What is the type of cancer?
Adenocarcinoma
What does necrosis represent? What is the most common cause? What are three more features?
Energy Failure.
Most often caused by ischaemia
Cell lysis due to loss of electro-ionic potential
It is pathological
It is energy independent - it occurs regardless of energy level (as opposed to apoptosis)
Define Apoptosis
Planned energy dependent exit strategy
Cell contents are not released, they go into apoptotic bodies
How long is the oesphagus? What structures are near it?
25cm
Passes from Cricoid to Cardia of stomach through the Diaphragm
What are the layers of the oesophagus?
Longitudinal muscular layer
Circular muscular layer
Submucosal layer
What do submucosal glands on biopsy indicate?
Tissue is from the oesophagus
How much fluid do submucosal glands produce?
1 litre of alkaline fluid a day
How does the oesophagus change in structure going down?
The top third is striated muscle.
The bottom third is smooth muscle.
The middle third is a mixture of both.
What lines the oesophagus?
What are the implications of this?
Stratified Squamous Epithelium
No infections - lots of layers of cells i.e. not every cell is in contact with the basement membrane.
You get oesophagitis though - it is a wear and tear organ, layers are shed and new layers of cells replace it.
Where does the stomach meet the oesophagus? Give a specific name.
Z-line i.e. Squamo-Columnar Junction
After this point you get columnar epithelium
Generally how do you get cancer of the oesophagus?
It becomes inflamed.
What are the two pathological mechanisms in oesophagitis?
Ulceration and Metaplasia
Both start with inflammation
In Ulceration, inflamation –> ulceration –> Loss of surface epithelium –> Repair –> Replacement of useful cells with myofibroblasts –> Scarring/Strictures
In Metaplasia, inflammation –> metaplasia –> metaplasia to columnar cells (±Goblet Cells) –> Dysplasia –> Cancer
What causes oesophagitis?
Reflux
Corrosives (e.g. bleach)
What are complications of oesophagitis?
Barrett’s Oesophagus: metaplastic columnar lined oesophagus ± goblet cells
Barrett’s –> Malignancy
Strictures due to fibrosis and scarring due to previous ulceration
Haemorrhage due to ulceration
Two distinct features of Barrett’s Oesophagus
Columnar Metaplasia
Columnar Metaplasia with Goblet Cells
Where are goblet cells found normally?
The small bowel
What do we call Columnar Metaplasia with Goblet Cells?
What are the implications
intestinal-type metaplasia
higher risk for future cancer than simple columnar type metaplasia
thus not all Barrett’s carries an equal risk. Do an OGD on patients with goblet cells more frequently.
What are the types of oesophageal malignancy?
What is their aetiology and epidimeiology?
Mid-Distal Oesophagus: SCC
Commonest Type Worldwide
Caused by Smoking and Boozing
Distal Oesophagus: Adenocarcinoma
Commonest Type UK
Caused by Columnar Epithelial Transformation
Caused by GORD/Oesophagitis/H.pylori
What is a common oesophageal pathology other than inflammation, malignancy and Barrett’s?
Oesophageal Varices
What is Oesophageal Varices?
extremely dilated sub-mucosal veins in the lower third of the esophagus
What causes Oesophageal Varices and what are the implications?
Any cause of portal hypertension
- cirrhosis
- portal vein thrombosis
- IVC obstruction
It can cause torrential GI bleeding
How to treat Oesophageal Varices?
Terlipressin
Resucitate with blood and crystalloids
Score them to find risk
Infuse with PPI
What type of cells line the stomach?
Columnar Epithelium
What are two specialised cells in the stomach? What functions?
Parietal Cells - produce acid
P Cells / Chief cells - produce pepsin –> pepsinogen (broken down by acid)
What do goblet cells in the stomach indicate?
Goblet Cells are NOT seen in the stomach
Indicated intestinal-type metaplasia
What causes Gastritis?
Give Acute and Chronic
Acute: Alcohol, NSAIDs, H. pylori, physiological stress e..g hypovolaemia (stomach is the most sensitive organ in GIT to ischaemia)
Chronic: ABCCC A: Autoimmune (pernicious anaemia) B: bacteria (H. pylori) C: Corrosives (bile reflux, NSAIDs) CMV ((Renal) Transplant Patients) Crohn's
What is pernicious anaemia?
Antibodies against intrinsic factor
Stops Vitamin B12 absorbtion
Causes Pernicious macrocytic aneamia
Most common cause of VitB12 deficiency in UK
BONUS: For what disease are 10% of our lymphocytes created for?
Implications?
CMV
thus transplant patients who are immunosupressed are at risk of CMV infection. esp. renal transplant patients.
4 Complications of Gastritis
Ulceration
Perforation
Haemorrhage
Cancer
What kind of bacteria is H. pylori? How does it get energy?
Gram Negative Curved Rod
Breaks down acid in the stomach using hydrogenase
What makes H. pylori outcome worse?
Cag pathogenicity Island
It is a toxin injected into the submucosa
What does H. pylori cause and what does this lead to?
Chronic Gastritis –> Ulcers and Scarring
Adenocarcinoma
LYMPHOMA
What is onr bacterial cause of Lymphoma?
H. pylori
What is the treatment of H. pylori?
One week of Triple Therapy
PPI (-razole)
Clartihromycin
Amoxicillin or Metronidazole
How does H. pylori cause Lymphoma?
Induces MALT –> Germinal Centre + Lymphoid Follicles –> Adenocarcinoma via columnar epithelium metaplastic change
What is MALT?
Mucosa Associated Lymphoid Tissue
What are the different types of Gastric cancer and what are their percentages?
Adenocarcinoma 95%
SCC, Lymphoma, GIST (Gastrointestinal stromal tumors( benign/malignant)) 5%
What are two features of adenocarcinoma?
Gland forming
Mucin Secretion
What are two features of Squamous Cell Carcinoma?
Keratin Producing
Intercellular Bridges
What are the two main types of adenocarcinoma? Describe them.
Intestinal (classic) and Diffuse
Intestinal: well-differentiated, mucin producing, gland forming = a classic adenocarcinoma
Diffuse: single-cell architecture, no gland formation, contains signet ring cell, spread extremely quickly
What is AKA a classic adenocarcinoma?
Intestinal Adenocarcinoma
What is a poorly differntiated adenocarcinoma?
Diffuse adenocarcinoma
What is a signet ring cell indicative of and how is it formed?
Diffuse Adenocarcinoma (pathagnomonic) Formed as these cells contain a lot of mucin which pushes the contents of the cell to the periphery, with the nucleus flush on one end
What type of epithelium is found in the duodenum?
intestinal-type epithelium
What is the villous crypt ratio?
> 2:1
What is a villi?
Villi are small, finger-like projections in the small intestine
What is a crypt?
These are folds inbetween villi. They are in the lamina propria layer and are mostly absorbative. They sometimes contain goblet cells.
What happens when there is damage in the small intestine?
Change in the villi:crypt ratio.
Shortening or blunting of villi
Crypts compensate by undergoing hyperplasia –> enlarged crypts
Ratio tends to –> 1:1 during inflammatory disease
Where are goblet cells seen and where are they definitely not expected to be?
Seen in the small intestine
Not normally seen in the stomach
What disease is most commonly caused by H.pylori?
Duodenal Ulcers
What are anterior and posterior (duodenal) ulcers?
Ulcers on the anterior aspect and posterior aspect of the duodenum respectively. (simple)
What are you worried about with anterior and posterior (duodenal) ulcers? What do you have to prepare for?
Anterior Ulcers –> perforate –> peritonitis
Posterior Ulcers –> Near Gastroduodenal Artery –> Haemorrhage –> more likely to require surgery
What causes a major haemorrhage from the small bowel?
Posteriorly sided duodenal ulcer
How to diagnose Coeliac Disease?
anti-endomysial Ab +ve
Anti-TTG +ve (tissue transglutaminase)
OGD on gluten diet
What pathological changes occur in Coeliac malabsorbption?
villous atrophy
crypt hyperplasia (hence reduction in villi:crypt ratio)
increased intraepithelial lymphocytes = CD8+ T cells
(20:100 lymphocytes: enterocytes or higher)
What can be difficult for patients when trying to diagnose them with Coeliac Disease?
Diagnosis requires 6 weeks of eating gluten before an OGD which can make patients feel very unwell
BONUS: What does ERCP stand for?
Endoscopic Retrograde Cholangio-Pancreatography
What are complications of Coeliac Disease?
Malabsorption
Deficiencies
Lymphoma EATL (Enteropathy Associated T-cell Lymphoma)
Treating Coeliac reduces risk of lymphoma