WRITTEN Qs Flashcards
What is the pathophysiology of Graves ophthalmopathy
TSH receptors are also expressed by orbital fibroblasts. As for Graves disease, these fail to be recognised as “self” and are presented by T cells to the immune system, resulting in activation of the cellular immune system as well as antibody-mediated with anti-TSHR antibodies forming.
This commences an inflammatory cascade. The orbital fibroblasts then differentiate into myofibroblasts or adipocytes. There is also increased hyaluronan production (a hydrophilic glycosaminoglycan).
All of this results in extensive hyaluronan infiltration into the peri-orbital fat and the orbital muscles along with insterstitial oedema and a persistent inflamed state.
Clinical symptoms of lid rectraction, proptosis, exopthalmous and complications of this.
Potentially vision-threatening.
Troisier’s sign
An enlarged left supraclavicular lymph node.
Also called Virchow’s node.
This should alert you to the possibility of an intra-abdominal cancer (gastric most common, then other GI, then HPB or gynae).
Anatomically, this is where the thoracic duct empties into the left subclavian vein.
Anatomy of the thoracic duct
The thoracic duct contains lymph and chyle, it drains most of the lymph in the body, other than the right arm, thorax, head and neck which drain through the right thoracic duct.
It is usually 45cm long and about 5mm in diameter.
Abdomen
From its origin at the cisterna chyli (at the level of T12), the thoracic duct ascends anterior to and to the right of the vertebral column, situated in between the aorta, and the azygos vein.[3] The thoracic duct traverses the diaphragm at the aortic hiatus[3] to enter the posterior mediastinum.[3]
Posterior mediastinum
It ascends the posterior mediastinum between the descending thoracic aorta (to its left) and the azygos vein (to its right),[4] and is situated posterior to the esophagus at the T7 vertebral level. It crosses the midline to the left side at about the T5 level, continuing to ascend. It then passes posterior to the aorta, and to the left of the oesophagus.[3]
Superior mediastinum
The thoracic ducts ascends into the superior mediastinum, reaching 2-3cm superior to the clavicle,[3] as high up as the C7 vertebral level.[5]
In the superior mediastinum, the thoracic duct is situated posterior to and to the left of the esophagus. It is situated between the visceral and alar fascia.[5] It passes posterior to the left common carotid artery, vagus nerve (CN X), and internal jugular vein.[3] At C7 level, it lies posterolaterally to the carotid sheath. From here, it passes anteroinferiorly to the thyrocervical trunk, and phrenic nerve.[5] It descends until reaching and draining at the venous angle.[3]
Fate
The thoracic duct usually[3] drains into the systemic (blood) circulation at the left venous angle where left subclavian and left internal jugular veins unite to form the left brachiocephalic vein.[2][3]
What are the anti-reflux mechanisms?
Mechanical and physiological.
The lower oesophageal sphincter and oblique gastric sling fibres. The sphincter maintains a continuous tonicity, mediated by acetylcholine, and relaxes with vagal mediation and nitrous oxide producing cells.
The crural hiatus with a slip of the right crura wrapping around the oesophagus. Undergoes some vagally-mediated relaxation during swallowing, but also contracts with abdominal musculature contraction to prevent reflux.
The gastro-oesophageal flap valve, created by having an adequate length of intra-abdominal oeosphagus and the acute angle of His. (oesophago-gastric angle). With gastric filling, this pinches shut the oesophagus by the greater curve compressing towards the lesser curve.
The gastric mucosal “roulettes” may act as insulating cushions that prevent reflux.
What is the pathophysiology of GORD?
Anatomical and physiological antireflux mechanisms are overcome.
This may be through anatomical disruption of the “flap valve” as well as attenuation of the crural fibres associated with a hiatus hernia.
Inadequate oesophageal emptying (motility disorder) or reflux during physiological LOS relaxation - also associated with HH.
Increased TLOSR (associated with gastric distension, part of vagally mediated reflex to allow belching)
Mucosal injury, widening of the interstitial space between mucosal cells, submucosal inflammation can cause myenteric plexus injury, impacting upon the control of the LOS and causing pain.
This mucosal injury with chronic acid exposure can lead to remodelling of the mucosa to intestinal type (columnar epithelium, Barrett’s).
Describe the virulence factors of H pylori
Helicobacter pylori is a micro‐aerophilic, Gram negative, slow growing, spiral shaped, and flagellated organism
Colonisation, evading host defence, inducing tissue injury.
Colonisation:
- flagella: allow mobility through viscous mucous into less acidic submucous layer
- H pylori synthesises urease constitutively. As urease hydrolyses urea to form ammonia and carbon dioxide, and ammonia can absorb acid to form ammonium
- Adhesins - H pylori binds selectively to gastric epithelium. On adhesion, it causes remodelling of the apical part of the cell and also initiates the inflammatory cascade
- Heat Shock Proteins - esp HP60 is associated with formation of MALT. These are HIGHLY ANTIGENIC
- Induction of hypchlorhydria - circulation of acid neutralising substances released by HP such as ammonia AND dysfunction of parietal cells with increased cananlicular permeability (H+ flows back into cell) and disruption of H/K/ATPase
Evading host defense:
- HP LPS is not as antigenic as some other bacteria, antibodies that form to the LPS may then come to attack gastric epiithelium through molecular mimicry – a possible mechanism for atrophic gastritis.
Causing host injury:
- cytotoxin release:
- VacA – associated with PUD, MALT and gastric cancer.
- CagA – binds to receptors on epithelium, then starts a cascade to increase IL-8 within cells, rearranges cytoskeleton. Probably also has a role in cancer. (moreso Eastern population)
HOST FACTORS likely play a role in how the disease presents. If a large parietal cell mass is present at time of infection, H pylori infection may be confined to the antrum and cause duodenal disease.
If parietal cell mass is sparse, likely to have corpus associated disease, leading to atrophy of parietal and chief cells and a precursor for cancer.
What interval should you use for surveillance of Barrett’s oesophagus based on findings of no dysplasia, indeterminate, low or high grade?
What is the Seiwert classification
- Type I
○ Tumour centre 1-5 cm above GOJ
○ Adenocarcinoma of distal oesophagus (usually from Barrett’s)
○ Present late with 75% with LN mets (mediastinal or coeliac LN)
○ May infiltrate GOJ from above- Type II
○ Arise at the GOJ
○ May extend upward 1cm proximal or downward 2cm distal to the GOJ - Type III
○ Centre of tumour lies 2-5cm below GOJ
○ Subcardinal gastric carcinoma (arise from proximal stomach)
○ Infiltrate GOJ from below
LN drainage to peri-gastric nodes
- Type II
