Gastrointestinal pathology (1) Flashcards
(91 cards)
1
Q
What is the generic histological structure of the GI tract?
A
2
Q
The structure of the GI tract is relatively constant throughout. Which of the 5 histological GI layers varies throughout the GI tract?
A
Mucosa
3
Q
Hence, describe the mucosal structure in the following:
- Oesophagus
- Stomach
- Small Intestine
- Colon + rectum
A
- oesophagus: white stratified squamous (a transit tube)
- stomach: red-brown thick glandular (storage + digestion)
- small intestine: glandular w/ villi (nutrient absorption)
- colon + rectum: glandular w/ crypts (water absorption)
4
Q
What is gastro-oeseophageal reflux?
A
- there is regurgitation of acidic gastric contents into lower oesophagus
- acid injures the squamous epithelium lining the oesophagus
- results in inflammation (reflux oesophagitis)
5
Q
What are the risk factors for developing GORD?
A
- obesity + pregnancy (inc intra-abdo pressure)
- smoking, alcohol, coffee consumption (lowers oesophageal sphincter tone)
- hiatus hernia
6
Q
What is a hiatus hernia?
A
- protrusion (or herniation) of the upper part of stomach
- into the thoracic cavity
- thought to be due to combo of diaphragmatic weakening + inc intra-abdo pressure
- the major clinical effect = weakening of lower oesophageal sphincter mechanism
7
Q
What is the presentation + associated complications of GORD?
A
- Heartburn (major feature) relieved by antacids
- Regurgitation -> waterbrash
- Belching
- Oeseophagitis
- Stricture (progressive dysphagia)
- Bleeding (haematemesis, melaena)
- Barrett’s oesophagus
- Nocturnal asthma + chronic cough
8
Q
A complication of GORD is Barrett’s oeseophagus (10%). What is Barrett’s oesophagus?
A
- when normal oeseophageal squamous epithelium replaced
- by metaplastic columnar mucosa
- form segment of ‘columnar-lined oeseophagus’
- an adaptive response to prolonged injury caused by GORD
- asymptomatic - most cases identified when pts undergo OGD (for GORD/dyspepsia)
9
Q
What % of those with Barrett’s Oesophagus progress to oeseophageal cancer?
A
- 0.1-0.4%
10
Q
What does metaplasia do to the squamous mucosa lining in the oesophagus?
A
Metaplasia in Barrett’s Oesophagus:
- Normal squamous mucosa replaced with glandular (columnar) mucosa
- Due to reflux of gastric acid (as the insult)
11
Q
What may the metaplastic columnar epithelium progress to next?
A
- Dysplasia (occurs in 2% of those with Barrett’s)
- And then into an invasive adenocarcinoma
- This is known as the metaplasia-dysplasia-carcinoma sequence
12
Q
Why and how is dysplasia identified and managed in patients?
A
- Bc development of oesophageal adenocarcinoma (malignant) is preceded by a phase of dysplasia (pre-malignant)
- some gastroenterologists perform surveillance endoscopy w/ biopsies at 3-5yr intervals to look for dysplasia
- if dysplasia identified, intervention (eg radiofrequency ablation or endoscopic mucosal resection) is advised
13
Q
What is characteristic of the adenocarcinoma that the dysplasia doesn’t demonstrate?
A
Invasion through the basement membrane
14
Q
Who is oesophageal cancer common in?
A
- 50-70yr age group
- M > F
15
Q
How does oesophageal cancer present?
A
- Progressive dysphagia (of solids first then liquids too)
- Weight loss
- Anorexia
- Lymphadenopathy
16
Q
What are the key investigations?
A
- endoscopy
-
biopsy
- type of cancer
- grade
17
Q
What is the most common type of oesophageal cancer in the UK?
A
- adenocarcinoma (70% of all new OCa diagnoses)
- marked rise in incidence in western world in last 30ys
- usually arises from Barrett’s mucosa in lower oesophagus
- remember that progression from Barrett’s -> cancer is not inevitable
- in fact, risk of dying from oesophageal adenocarcinoma in a pt with Barrett’s is 2% over 10 years (less than the risk of dying from ischaemic heart disease!)
18
Q
What is the second most common type of oesophageal cancer in the UK?
A
- squamous cell carcinoma
- most common type in other parts of world eg. china, japan
- oesophageal squamous cell carcinoma arises from native oesophageal squamous epithelium
- important risk factors for its development = smoking + alcohol
19
Q
How is oesophageal cancer staged?
A
- TNM system
- performed using range of techniques
- eg. EUS, chest/abdo CT, laparoscopy
20
Q
What is discussed at an MDT meeting for oesophageal cancer?
A
- decide on most appropriate treatment
- curative intent (surgery with/without neoadjuvant therapy)
- palliative intent (eg. dilatation, stenting, radiotherapy etc)
21
Q
What is the prognosis for oesophageal cancer?
A
- 5-10% survival at 5 years
- this is mainly bc tumor is usually at high stage on presentation
22
Q
What is gastritis?
A
- strictly speaking, refers to inflammation in stomach
- however, in clinical practice it is often used to describe any redness of the gastric mucosa seen at endoscopy
23
Q
What are 2 important causes of gastritis?
A
- NSAIDs
- Helicobacter Pylori infection
24
Q
What is H. Pylori and how does it survive?
A
- gram negative bacteria that colonises stomach
- spread by oral-oral or faecal-oral transmission
- it lives in the thick mucus layer on mucosal surface
- H. pylori synthesises urease, which catalyses conversion of urea to ammonia. The ammonia neutralises the gastric acid and thus improves survival of the bacteria
25
Gastric *H. Pylori* is associated with a range of consequences, such as?
* \> 80% of pts have an **asymptomatic** mild chronic gastritis
* a minority of pts develop symptomatic **gastritis**
* a minority of pts develop a **peptic ulcer**
* a small minority of pts develop gastric **carcinoma**
* a v small minority of pts develop gastric **lymphoma**
26
What is a peptic ulcer?
* _breach in mucosa_ of the **lower oesophagus, stomach** or **duodenum**, _extends through full thickness of mucosa_ and in addition **_may_** extend into the submucosa or deeper layers of wall
* fails to heal over a reasonable period of time
* most comonly located in the gastric antrum or proximal duodenum
27
What is the commonest cause of **gastric** and **duodenal** peptic ulcers?
* ***H pylori* gastritis**
* **NSAIDs**
* also: alcohol, smoking + stress
28
What is a Curling (stress) ulcer?
* seen in pts with massive trauma, extensive burns, sepsis, raised intracranial pressure or shock
* thought to arise as a consequence of mucosal ischaemia leading to inc susceptibility to acid pepsin injury
29
What is the commonest cause of **oesophageal** peptic ulcers?
Gastro-oesophageal reflux
30
Are peptic ulcers due to cancer?
No, they are a good example of chronic inflammation
31
**How** are peptic ulcers a good example of chronic inflammation?
there is simultaneous:
* **persistent tissue injury** + destruction at surface
* on-going inflammatory response to limit damage
* the main inflammatory cells are **macrophages**, **lymphocytes** and **plasma cells**
* attempts to organise and **heal by fibrosis** (scarring)
32
What is the pathogenesis of peptic ulceration?
* mucosal surfaces normally coming into contact w/ gastric acid + pepsin have evolved a # of **defence mechanisms**
* surface-adherent **mucus/bicarb layer**, **epithelial cell defences** + **mucosal blood flow**
* peptic ulcers can occur by **weakening** of these defence mechs or by **increased acid** attack
* surface mucus is significantly disrupted by *H pylori*
* epithelial cell defences are undermined by the cytotoxic effects of *H pylori* and NSAIDs
* mucosal blood flow alterations probs more important in _acute ulcers_ occurring in clinical states of shock
33
What is Zollinger-Ellison syndrome + how does it lead to peptic ulceration?
* tumours from pancreas, stomach or duodenum secrete large amounts of **gastrin** (gastrinomas)
* _cause excess gastric acid secretion_
* therefore increased acid attack -\> weakened defence system against peptic ulcer
34
What are complications of peptic ulcers?
* bleeding
* perforation
* stricture formation
* malignant change
35
How do _acute_ bleeds of peptic ulcers present?
* when an ulcer erodes wall of a large vessel, tend to be large
* presents with melaena or haematemesis
36
How does _chronic_ bleeding from peptic ulcers present?
* typically multiple smaller bleeds (compared to acute)
* over a long period of time
* may present as **anaemia**
37
What is the term used to describe when a peptic ulcer erodes through _all_ the layers of the wall? How does this present?
* **perforation**
* present as **peritonitis**
38
How might stricture formation due to peptic ulcer present?
* due to healing of the ulcer by fibrosis
* may present as obstruction
39
Is the development of carcinoma a common complication of peptic ulcers?
* No, it's rare
* in fact, it's now believed that reports of malignant transformation in peptic ulcers probably represents cases in which a lesion thought to be a chronic peptic ulcer was actually an ulcerated carcinoma from start
* ulcerated gastric carcinomas typically have a **rolled edge**
40
What investigation should be done from any suspected peptic ulcer in the **oesophagus** or **stomach** to rule out that it isn't actually an ulcerated cancer?
**Biopsy**
NB. _Dudoenal_ cancer is v rare and so chance of duodenal cancer masquerading as a peptic ulcer is remote. Hence duodenal ulcers do not need to be biopsied to exclude malignancy unless there are worrying endoscopic features.
41
Who is gastric cancer common in? Has the incidence changed?
* peak incidence in over 50yr age group
* M \> F
* incidence has fallen in west over last 50yrs
* reduction due to falling prevalence of ***H pylori*** infection and an **improved diet**
42
What are important risk factors for developing gastric cancer?
* ***H Pylori*** infection (but remember, most ppl w ***H Pylori*** infection will not develop cancer)
* cigarette smoking
* alcohol
* diet: food w/ nitrates/nitrite components; salt-based preservatives
* autoimmune gastritis
43
How might gastric cancer present?
* history of new-onset **dyspepsia** (esp in a pt \>55y)
* _unintended_ **weight loss**
* progressive **dysphagia**
* **vomiting**
* **Virchow's node** palpable (left supraclavicular fossa) - *Troiser's sign*
44
What kind of cancer are gastric cancers?
* **adenocarcinomas**
* arising from glandular mucosa
45
What are the 2 main types of gastric adenocarcinoma and how do they differ?
* **intestinal-type adenocarcinomas** - show gland formation, lined by mucus-secreting cells. _Better_ prognosis than diffuse-type (but still poor 5 year survival). Tend to occur in **older** individuals.
* **diffuse-type adenocarcinomas** - consist of 'signet-ring' cells, with a diffuse pattern of infiltration. Very aggressive -\> **v bad prognosis**. Tends to occur in a **younger** age group.
46
They key investigation for gastric cancer is endoscopy and biopsy. What important info does biopsy give us?
* **type of cancer** (usually squamous cell carcinoma or adenocarcinoma)
* the **_grade_** - well, moderately or poorly differentiated
47
How is gastric cancer staged?
* TNM system
* performed using a range of techniques
* eg. chest/abdo CT, staging laproscopy
48
All pts with gastric cancer are discussed at the MDT meeting to decide on most appropriate treatment: curative or palliative. What is the prognosis of gastric cancer?
* _very poor prognosis_
* around 5% survival at 5 years
* mainly bc tumour is usually at high stage on presentation
49
How much of the adult Western population develop gallstones?
* 10-15%
* Each year approx 2-4% of ppl with gallstones develop symptoms, in other words most people are asymptomatic
50
What is the pathogenesis of gall stones?
Normally cholesterol is solubilised in bile as a micelle with bile salts.
An imbalance between the proportions of cholesterol and bile salts lead to precipitation of the excess component as gallstones.
51
What are the 3 types of gallstones?
* **cholesterol stones** (20%) - large, yellow
* **billirubinate stones** (5%) - small, pigmented (dark)
* **mixed stones** (75%) - Ca salts, bile pigment + cholesterol
52
What are the risk factors for **cholesterol gallstone** formation?
* female sex
* obesity
* middle-age
* family history
all are associated w inc levels of cholesterol -\> results in imbalance between cholesterol + bile salts and the precipitation of gallstones
53
What link does Crohn's disease have to gallstones?
* Crohn's predisposes to development of gallstones
* Due to malabsorption of bile salts from terminal ileum
* Affected individual becomes depleted in bile salts
* They do not have enough bile to maintain the cholesterol dissolved in bile
* Thus cholesterol stones form
54
What can cause bilirubinate gallstones?
* **Haemolytic anaemias**
* Cause inc bilirubin production (bc of XS breakdown of Hb)
* Results in an imbalance between cholesterol + bile salts
* Thus, the bile salts precipitate as gallstone
55
What investigations can be done for gallstones?
* Ultrasound of gallbladder -\> identify 90% of gallstones
* Liver function tests to assess liver fxn
56
What ducts meet to form the common bile duct?
* Cystic duct from gallbladder
* Common hepatic duct (from R + R hepatic ducts)
* Come together to form common bile duct (outside the liver)
57
Remember, most patients with gallstones are asymptomatic. How might patients with symptomatic gallstones present?
* Biliary colic or cholecystitis (\>90% of symptomatic presentations)
* Jaundice +/- ascending cholangitis
* Acute pancreatitis
* Gallstone 'ileus'
58
How does a biliary colic come about and how does this present?
* if a gallstone impacts in + obstructs the _cystic duct_
* the gallbladder will **contract against** the acutely obstructed duct
* resulting in symptoms of biliary colic:
* upper abdo/RUQ pain, may radiate to back/tip of scapula, often nausea + vomiting
59
How does acute cholecystitis develop from a gallstone?
* if the impacted stone occludes cystic duct for a _prolonged period of time_
* it will rub + _damage_ the mucosal lining
* thereby inciting an **acute inflammatory response** in gallbladder wall
* there is development of acute cholecystitis
* **presence of fever** indicates **acute cholecystitis** (or cholangitis)
60
What is acute acalculous cholecystitis?
* acute cholecystitis _without_ gallstones
* thought to result from **ischaemia**
* the cystic artery is an end artery w/ no collateral circulation
* it occurs in pts who are hospitalised for conditions unrelated to gallbladder eg. hypotension + multiorgan failure; major trauma/burns; infections
* clinical symptoms tend to be insidious since they are obscured by underlying condition
* a high % of pts have no symptoms referable to gallbladder; diagnosis therefore rests on a high index of **suspicion**
* as a result of either delay in dx or disease itself, incidence of **gangrene + perforation** is much higher in _acalculous_ cholecystitis than cholecystitis due to gallstones
61
What is chronic cholecystitis?
* **repeated episodes** of biliary colic + acute cholecystitis
* results in chronic inflammation w/ **healing by fibrosis**
* as a consequence, gallbladder wall becomes _thickened_ + the _gallbladder shrinks_ in size
62
How do gallstones cause jaundice?
* if a gallstone impacts + obstructs the **_common bile duct_** (choledocholithasis), it will cause obstructive jaundice
* the jaundice develops bc bile is unable to drain into the duodenum for excretion
63
A serious complication of a gallstone obstructing the common bile duct is the development of **ascending cholangitis**. What is this?
* **inflammation of common bile duct**
* the biliary obstruction causes _stasis_
* predisposes to superimposed infection: gut bacteria (usually gram negative eg. E coli, Klebsiella) gain entry to biliary tree via **ampulla of Vater**
64
How does ascending chlangitis typically present clinically?
* **Charcot's triad**
* _jaundice_, _fever_ (usually w rigors) + _RUQ pain_
65
What happens if ascending cholangitis is left untreated?
* infection may ***_ascend_*** up to the liver
* causing **abscesses**
* and/or cause **sepsis**
* serious condition if left untreated has a high mortality
66
_Gallstones are the commonest cause of acute pancreatitis_. How do gallstones cause acute pancreatitis?
* if gallstone passes down common bile duct
* _obstructs_ **Ampulla of Vater**
* results in pancreatitis
* there is reflux of pancreatic secretions back up the pancreatic duct -\> pancreatic autodigestion -\> pancreatitis
67
What is the other major cause of pancreatitis apart from gallstones?
alcohol
68
What is gallstone 'ileus'?
* When a large gallstone causes **small bowel obstruction**
* Stone erodes through gallbladder into duodenum; then obstructs terminal ileum
* Gallstone enters the small bowel via a **fistula**, which forms between the inflamed wall of GB and a loop of small bowel
69
Why is gallstone 'ileus' a misnomer?
* Ileus is characterised by _cessation_ of normal peristaltic movements of bowel, typically a rxn of the bowel to any form of irritation around it (eg. post-op, peritonitis)
* If a gallstone obstructs the small bowel, the small bowel proximal to the obstruction will attempt to overcome the blocokage by _vigorous peristalsis_
## Footnote
*Hence, the term gallstone 'ileus' is incorrect*
70
What is the clinical presentation of gallstone ileus?
Cardinal features of bowel obstruction
* colicky abdo pain
* vomiting
* abdominal distension
* absolute constipation
71
What does Courvoiser's Law state and why?
*"In a jaundiced patient, the presence of a palpable gallbladder means that the jaundice is unlikely to be due to gallstones impacted in the biliary system"*
* bc a pt w/ jaundice due to gallstone in the common bile duct is likely to have a **fibrotic shrunken gallbladder** bc of repeated episodes of biliary colic + acute cholecystitis - as a consequence, the gallbladder is impalpable
* a patient w/ jaundice due to another cause _may_ have a palpable gallbladder
72
What is another cause of a palpable gallbladder, unrelated to gallstones?
Often (but not necessarily) cancer of the head of the pancreas
73
What are the two broad functions of the pancreas?
* **Exocrine** - secreting digestive enzymes into the pancreatic duct system
* **Endocrine** - secreting hormones such as insulin and glucagon directly into the blood
74
What is the most common type of pancreatic cancer?
* **Adenocarcinoma**
* Arises from glandular duct cells that line ducts of exocrine system
75
Who is pancreatic adenocarcinoma common in?
* Elderly males
* Very little is known about underlying cause
* **Smoking** is only well recognised risk factor
76
Most pancreatic adenocarcinomas involve the head of the pancreas. What do they present with?
* **Obstructive jaundice**
* tumour compresses common bile duct as it passes through the head of pancreas so that bile is unable to drain into duodenum
* other features: **weight loss**, **mid-epigastric pain** (often radiating to back)
77
What is the treatment for majority of pancreatic carcinoma patients?
* 80% of pts with pancreatic carcinoma have **advanced disease** (high stage) at time of dx
* _treatment is palliative_
* palliative treatment options:
* chemotherapy
* stenting the common bile duct to relieve jaundice
* optimising symptom control
78
A minority of pancreatic carcinoma patients (20%) are suitable for curative surgery - Why are they suitable? What is the procedure called?
* bc tumour appears to be confined to pancreas and lymph nodes are not involved
* **Whipple's** procedure
79
What happens in a Whipple's procedure?
The **distal stomach, gallbladder, common bile duct, head of pancreas, duodenum, proximal jejunum** and **regional lymph nodes** are resected.
Reconstruction restores intestinal fxn by re-establishing flow of pancreatic juices, bile and food along GI tract.
80
What is the 5 year survival following a) curative surgery (Whipple's) and b) overall survival for pancreatic cancer?
A) Whipple's - **20-40%**
B) **5%** (incl majority of pts who have advanced disease)
81
How common is Coeliac disease?
Affects ~ 1% of UK population
82
What is Coeliac disease?
* intolerance to **gluten**
* in particular, **gliadin**, the alcohol-free fraction of gluten, is the disease-producing component
* gluten is found in wheat, barley and rye
83
What is the **brief** pathogenesis of coeliac disease?
* not fully understood
* thought that gliadin triggers inappropriate activation
* of intestinal T cells
* in genetically susceptible individuals (ppl w/ HLA-DQ2 and HLA-DQ8 haplotypes)
* resulting in damage to epithelial cells
84
Now explain in more detail what happens in patients with coeliac when gluten is digested in comparison to a healthy individual?
* **gluten** digested by luminal and brush-border enzymes in small intestine
* into aino acids + peptides, incl 33AA **gliadin** peptide
* gliadin is **deamidated** in mucosa by **tissue transglutaminases** (tTG)
* in those w/ HLA-DQ2 and HLA-DQ8 haplotypes, deamidated gliadin closely _fits_ the **MHC II grooves**
* gliadin presented to **T helper cells** by antigen presenting cells
* initiates a **Th2-predominant immune response**
* generates **cytotoxic T cells** _against_ gliadin
* cytotoxic T cells migrate into intestinal epithelium, visible on biopsy as intraepithelial lymphocytes
* the T cells damage + destroy epithelial cells resulting in progressive villous atrophy
* as a result, crypts become **hyperplastic** to compensate for cell loss
* loss of normal small bowel fxn -\> malabsorption
* also a **humoral immune response** w/ generation of **antigliadin**, **antiendoymysial** and **antiTTG** antibodies - useful antibodies diagnostically
85
What is the clinical presentation of coeliac disease?
* at _any age_, most commonly in childhood or middle age
* symptoms of **malabsorption** (diarrhoea, steatorrhoea, weight loss, lethargy, bloating, abdo pain)
* non-specific symptoms: eg. anaemia (usually iron def), irritable bowel syndrome-like symptoms, altered bowel habit, abdo pain
* in children, coeliac disease is an important cause of failure to thrive and delayed puberty
* an intensely itchy and blistering rash over elbows + buttocks - **dermatitis herpetiformis**
* some pts are asymptomatic and diagnosis is discovered incidentally
86
How is coeliac disease diagnosed?
* **history** and **examination**
* gluten-containing diet better to be consumed during diagnostic process
* serology tests: **total IgA and IgA tissue transglutaminase** antibodies are currently the preferred first line test (owing to its high sensitivity and negative predictive value)
* **IgA anti-endomysial** (EMA) antibodies can be used if IgA tTG is weakly positive
* _gold standard_ ix: **endoscopy and duodenal biopsy**
87
What does tissue biopsy for positive coeliac show?
* **villous atrophy**
* **crypt hyperplasia**
* **prominent intraepithelial lymphocytes**
Generally agreed that duodenal biopsy should be performed on all adult patients to confirm the diagnosis
88
What is the treatment for coeliac?
* **Life-long gluten-free diet**
* Those with coeliac disease (+ fam members, carers) should be given sources of info on the disease, including a national and local specialist coeliac groups and dietiticans with a specialist knowledge of coeliac disease
89
What are complications of coeliac disease?
* Malabsorption (-\> anaemia + deficiencies)
* Osteopenia/osteoporosis
* Dermatitis herpetiformis
* Lymphoma
90
Why do patients with coeliac develop osteopenia/osteoporosis? How can this be investigated and treated?
* most pts w/ coeliac disease are **osteopenic** (reduced bone density)
* bc they fail to reach their peak bone mass during young adult life
* due to _malabsorption of calcium_
* reduction in bone density is usually mild, most pts are only osteopenic
* however, some are actually **osteoporotic** w/ associated risk of fracture
* at dx, pts given lifestyle advice + basline **DEXA** scan to assess bone mineral density
* pts should maintian adequate calcium and vit D intake
* a gluten-free diet should prevent further bone loss and may improve bone density
91
Why do coeliac patients develop dermatitis herpetiformis?
* intensely itchy chronic blistering skin condition
* typically occurs symmetrically on extensor surfaces (buttocks, back of neck, knees, elbows etc)
* it's _not_ related to herpes virus
* rather, associated w/ coeliac disease although exact mechanism not fully understood
* **may be due to autoantibodies to _epidermal_ transglutaminase**
