Hamzah's GI pathology Flashcards
1
Q
What is Crohn’s disease?
A
Chronic idiopathic inflammatory bowel disease characterised by transmural granulomatous inflammation`
2
Q
Aetiology of Crohn’s disease
A
Unknown
CARD15 possible gene mutation
smoking increases risk
host immune response
3
Q
Risk factors for Crohn’s disease
A
FH, smoking
4
Q
Macroscopic pathology of Crohn’s disease
A
- affects any part of GI tract
- skip lesions - discontinuous GI involvement
- Deep ulcers and fissures in mucosa – cobblestone appearance
5
Q
Microscopic pathology of Crohn’s
A
- Transmural inflammation – spans full depth of intestinal wall
- Granulomas present in 50%
6
Q
Epidemiology of Crohn’s
A
- Usually presents in teenagers and people in their 20s
- 40 IBD patients / 100,000 patients (UK)
7
Q
Symptoms of Crohn’s
A
Urgent diarrhoea, abdominal pain, weight loss, fever, malaise, anorexia
8
Q
Signs of Crohn’s
A
o Abdominal tenderness/mass o Perianal skin tags/abscesses/fistulas o Aphthous ulcerations o Clubbing o Skin, joint and eye problems
9
Q
Complications of Crohn’s
A
Small bowel obstruction, fistulae, abscess formation, perforation, fatty liver, colon cancer, renal stones, malnutrition
10
Q
Differential diagnosis of Crohn’s
A
UC, TB, carcinoid, amyloidosis, infective diarrhoea, IBS
11
Q
Diagnostic tests for Crohn’s
A
- Blood = FBC, ESR, CRP, U&es, LFT, INR, ferratin
- Stool = MC&S to exclude C. diff, E. coli
- Colonoscopy and rectal biopsy
- Small bowel enema = identifies ileal disease
12
Q
Treatment of mild attacks in Crohn’s
A
oral prednisolone, review in clinic (lower dose every few weeks if symptoms are improving)
13
Q
Treatment of severe attacks in Crohn’s
A
- IV steroids –> hydrocortisone
- Treat rectal disease –> steroids
- Metronidazole
- blood transfusion
- TNF-alpha inhibitors - infliximab can decrease disease activity
14
Q
Treatment of perianal disorders
A
- oral abx
- immunosuppressants and infliximab
- local surgery
immunosuppressant - azathioprine
15
Q
Surgery in Crohn’s
A
NOT CURATIVE
temporary ileostomy, resection of part of normal bowel
16
Q
Why is bypass and patch surgery not done in Crohn’s?
A
widespread disease –> high risk of recurrence
17
Q
What is UC?
A
A relapsing and remitting inflammatory bowel disease that is restricted to the large bowel mucosa.
Always involves the rectum and extends proximally
18
Q
UC just rectum
A
proctitis
19
Q
UC with left colon
A
left-sided colitis
20
Q
UC entire colone
A
pancolitis
21
Q
What does UC never pass?
A
ileo-cecal valve
22
Q
Aetiology of UC
A
- unknown
- abnormal mucosal response to luminal bacteria
23
Q
Is smoking protective in UC
A
YES
24
Q
Epidemiology of UC
A
- Most cases present in individuals between the ages 15-30
- 3x as common in non-smokers
25
Risk factors for UC
history, ethnicity (White and Ashkenazi Jews)
26
Pathophysiology of UC
- Pseudo polyps and hyperaemic/haemorrhagic granular colonic mucosa formed by inflammation
- Punctate ulcers may extend deep into lamina propria
- Different from Crohn’s disease as it is not a transmural disease. (UC=mucosal disease)
- No skip lesions
- Red mucosa – bleeds easily
- No granulomata
- Goblet cell depletion
- Crypt abscesses
27
Symptoms of UC
o Episodic/chronic diarrhoea with blood/mucus
o Crampy abdominal discomfort
o Bowel frequency relates to severity (>6 motions = severe)
o Urgency/tenesmus = proctitis
o Systemic symptoms in attacks = fever, malaise, anorexia, weight loss
28
Signs of UC
o May be none
o Acute severe UC = fever, tachycardia, distended abdomen
o Extraintestinal signs = clubbing, aphthous oral ulcers, joint arthritis, fatty liver, amyloidosis
29
Differential diagnosis of UC
Crohn's, laxative abuse, infective colitis, colonic polyps
30
DT for UC
Blood - FBC, U&E, ESR, CRP, LFT
Stool - MC&S (C. diff)
AXR - mucosal thickening, colonic dilatation
Erect CXR - perforation
Colonoscopy - allows biopsy - mucosal ulcers, crypt abscesses, goblet cell depletion
31
Complications of UC
- perforation and bleeding
- toxic megacolon venous thrombosis
- colonic cancer
32
What is the goal for treatment in UC?
induce and maintain remission
33
Treatment of mild UC
- mild = less than 4 stools per day
- 5-aminosalicylic acid
- steroids - prednisolone (PR)
34
Treatment of moderate UC
- moderate = 4-6 stools per day
| - oral prednisolone and 5-aminosalicylic acid and twice daily steroid enemas
35
Treatment of severe UC
- severe = more than 6 motions per day
- hospital admission - nil by mouth, IV hydration
- IV hydrocortisone
- rectal steroids
36
What do you give when there is improvement in UC?
5-aminosalicylic acid and prednisolone
37
What do you give when there is no improvement in UC?
colectomy
38
Surgery in UC
- proctocolectomy and terminal ileostomy
| - colectomy with ileo-anal pouch
39
Drug for maintaining remission of UC for life
5ASA for life
40
What is IBS
a mixed group of abdominal symptoms for which no organic cause can be found
41
Aetiology of IBS
F:M = 2:1
| Age at onset = <40 days
42
Diagnosis of IBS requires
- pain/discomfort relieved by defecation
- altered stool form/bowel frequency
- urgency, incomplete defecation, abdominal bloating distension, mucus PR, worsening of symptoms after food
43
Other symptoms of IBS
nausea, bladder symptoms, back ache
44
What exacerbates IBS?
stress, menstruation, gastroenteritis
45
Signs of IBS
general abdominal tenderness / normal examination
46
Differential diagnosis of IBS
colon cancer, IBD, coeliac disease, gastroenteritis
47
Diagnostic tests for IBS
- FBC, CRP, ESR, U&Es
- Coeliac screen
- Serum CA-125 to exclude ovarian cancer
- Faecal calprotectin = marker of bowel inflammation, raised in IBD
- Colonoscopy if over 60 and any marker of organic disease
48
Treatment of IBS
- Healthy diet - fibre, lactose, fructose, fizzy drinks, caffeine
- constipation - lactulose
- diarrhoea - loperamide
- for bloating - oral antispasmodics - mebeverine
49
What is coeliac disease?
An autoimmune disorder caused by an abnormal immune response to dietary gluten
50
What happens to the mucosa of the duodenum and jejunum in coeliac disease?
villous atrophy and malabsorption
51
What is gluten found in?
wheat, rye and barley
52
What triggers the immune response in coeliac disease?
Gliadin
53
Pathogenesis of coeliac disease
- Associated with HLA class 2 molecules DQ2 (95% of cases) and DQ8
o Alpha-gliadin peptide is the toxic portion of gluten
o Alpha-gliadin is resistant to proteases in the small intestine lumen
o It passes through the cell membrane by binding to transferrin receptors on enterocytes
o Its deaminated by tissue transglutaminases and becomes negatively charged
o This then binds to APCs in the lamina propria via HLA-Dq2
o This activates gluten-sensitive T cells
o Inflammatory cascade and mediator release leads to VILLOUS ATROPHY and CRYPT HYPERPLASIA
54
Epidemiology of coeliac disease
- common in Irish
| - peaks in infancy and 50-60 year olds
55
Symptoms of coeliac disease
50% = asymptomatic
children = failure to thrive, bloating, diarrheoa
o Diarrhoea, steatorrhea, abdominal pain, bloating, nausea/vomiting, weight loss, fatigue
56
Signs of coeliac disease
- Dermatitis herpetiformis, osteomalacia, aphthous ulcers, angular stomatitis
57
Differential diagnosis of coeliac disease
IBD, IBS, lactose intolerance
58
Diagnostic tests for coeliac disease
- Bloods – FBC, low Hb, mild anaemia, iron deficiency, folate deficiency (folate is absorbed in the ileum bound to intrinsic factor which is released by parietal cells)
- IgA anti-transglutaminase (tTG) antibodies = highly sensitive
- IgA endomysial (EMA) antibodies = less sensitive
- Duodenal biopsy --> crypt hyperplasia, villous atrophy, inflammatory cells in lamina propria
- DEXA scan
59
Treatment of coeliac disease
lifelong gluten free diet
- eat rice, potatoes and oats
- can be prescribed gluten free food
60
Complications of coeliac disease
- Anaemia
- Dermatitis herpetiformis
- Osteoporosis
- Increased risk of malignancy
- Secondary lactose intolerance
- Hyposplenism
61
What is GORD?
reflux of stomach contents causing symptoms
62
What can prolonged reflux cause?
- oesophagitis
- benign oesophageal strictures
- Barrett's oesophagus
63
Aetiology of GORD
LOS hypotension, hiatus hernia, loss of oesophageal peristaltic function, obesity, HCl hypersecretion
64
Risk factors for GORD
Overeating, smoking, alcohol, pregnancy, surgery in achalasia, drugs – CCBs, BBs, tricyclic antidepressants=amitriptyline, H. pylori? (eradication may help symptoms)
65
Pathophysiology of GORD
- LOS tone is reduced and there are frequent transient LOS relaxations
- Increased mucosal sensitivity to gastric acid
- Reduced oesophageal clearance of acid
- Delayed gastric emptying and prolonged post-prandial and nocturnal reflux also contribute
66
Oesophageal presentation of GORD
o Heartburn --> burning, retrosternal discomfort after meals, lying down or straining, relieved by antacids
o Belching
o Acid brash – acid/bile regurgitation
o Water brash – massively increased salivation --> mouth fills with saliva
o Odynophagia (pain when swallowing)
67
Extra-oesophageal presentation of GORD
o Nocturnal asthma
o Chronic cough
o Laryngitis – hoarseness, throat clearing
o Sinusitis
68
Complications of GORD
oesophagitis, ulcers, benign stricture, iron deficiency, metaplasia (oesophageal cancer)
69
Differential diagnosis of GORD
-Cardiac disease, sphincter of Oddi malfunction, duodenal/gastric ulcers or cancers, oesophageal spasm, oesophagitis from NSAIDs, herpes, Candida
70
Diagnostic tests for GORD
- Endoscopy if >55 with alarm symptoms (weight loss, anaemia, haematemesis)
- Barium swallow --> may show hiatus hernia
- 24hr oesophageal monitoring and oesophgeal manometry (motility study)
71
Lifestyle treatment in GORD
weight loss, avoid excess alcohol, hot drinks and spicy food, smoking cessation, small regular meals, raise bed head
72
Drug treatment in GORD
- Antacids - sodium bicarbonate
- Alginates - Gaviscon
- PPIs- lansoprazole
- H2 receptor antagonists - ranitidine
73
Surgery in GORD
laparoscopic Nissen fundoplication - fundus is wrapped around lower oesophagus - increases resting LOS pressure
74
What is an ulcer?
a breach in the mucosal surface
75
where can peptic ulcers occur?
oesophagus, stomach or proximal duodenum
76
What cells are in the fundus and gastric body?
parietal and chief cells
77
What cells are predominantly found at the gastric antrum?
G cells - release gastrin when food enters the stomach
78
Where are Brunner glands found?
duodenum - secrete mucus
79
Aetiology of peptic ulcers
- H. pylori infection
- NSAIDs
- Zollinger-Ellsion syndrome
80
How does H. pylori cause peptic ulcers?
colonises gastric mucosa
- releases adhesions - proteases --> damage mucosal wall
- damage starts in gastric antrum
81
How do NSAIDs cause peptic ulcers?
- inhibit cyclooxygenase (helps synthesis inflammatory prostaglandins)
- gastric mucosa becomes susceptible to damage
82
How does Zollinger-Ellison syndrome cause peptic ulcers?
- gastrinoma
| - Neuroendocrine tumour which secretes abnormal amounts of gastrin --> excess HCl production
83
Risk factors for duodenal ulcers
H. pylori, drugs (NSAIDs, steroids, SSRIs), smoking
84
Risk factors for gastric ulcers
H. pylori, smoking, NSAIDs
85
Where do gastric ulcers typically occur?
lesser curvature of the stomach
86
Where do duodenal ulcers typically occur?
just after the pyloric sphincter and Brunner gland hypertrophy is present
87
Clinical presentation of peptic ulcers
- Gastric ulcer - pain increases when eating --> weight loss
- Duodenal ulcer - pain decreases when eating --> weight gain
- epigastric pain often relieved by antacids
- bloating
- fullness after meals
- heartburn - retrosternal pain and reflux
- tender epigastrium
88
ALARM symptoms
```
Anaemia (iron deficiency)
weight loss
anorexia
progressive symptoms
haematemesis
swallowing difficulty
```
89
Differential diagnosis of dyspepsia (indigestion)
GORD, gastric malignancy, duodenitis, gastritis
90
Diagnostic tests for peptic ulcers
- <55 --> non-invasive H. pylori tests = 13C-urea breath test, stool antigen test
- Upper GI endoscopy and biopsy (centre and edge of ulcer to establish if benign or malignant)
- barium meal --> detect gastric outlet obstruction
91
H. pylori positive treatment of peptic ulcers
clarithromycin, amoxicillin and PPI
| - Eradication confirmed with stool test/breath sample
92
H. pylori negative treatment of peptic ulcers
stop NSAIDs, steroids
| Treat with PPIs
93
Complications of peptic ulcers
- bleeding - can erode into left gastric artery or gastroduodenal artery
- perforation - duodenal ulcers can perforate and lead to air under diaphragm --> referred pain at right shoulder
- gastric outflow obstruction - duodenal ulcers near pyloric sphincter can cause scarring and obstruction of gastric emptying
- malignancy
94
What is appendicitis?
inflammation of the appendix
95
What is the highest incidence of appendicitis?
between 10-20 year olds - most common GI surgical emergency
96
Aetiology of appendicitis
- Faecolith - stone made of faeces
- lymphoid hyperplasia
- filarial worms
97
Risk factors for appendicitis
FH, more common in males
98
Differential diagnosis of appendicitis
UTI, cystitis, Crohn's disease, perforated ulcer, diverticulitis, cholecystitis
99
Pathogenesis of appendicitis
- Gut microorganisms (E. coli) invade the appendix wall after lumen obstruction
- Appendix keeps secreting mucus --> increases the psi within the appendix and it enlarges and irritates visceral nerve fibres and blood vessels, This leads to ischaemia of the appendix wall and the appendix can no longer secrete mucus --> microorganisms can now invade the appendix wall
100
Clinical presentation of appendicitis
- Periumbilical pain that moves to right iliac fossa
- Anorexia
- Constipation (but diarrhoea can occur)
- General signs = tachycardia, fever, furred tongue, coughing hurts, foetor and flushing, shallow breathing
- RIF signs = guarding, rebound and percussion tenderness, PR painful on right
101
Diagnostic tests for appendicitis
- Rovsing’s sign = pain greater in RIF than LIF when LIF is pressed
- Psoas sign = pain on extending hip
- Cope sign = pain on flexion and internal rotation of right hip
- Blood tests = neutrophil leucocytosis, elevated CRP
- Appendix is not always visualised with US
- CT
102
Treatment of appendicitis
- prompt appendectomy
- antibiotics - piperacillin and tazobactam
- laparoscopy can be used (high xp surgeon needed)
103
complications of appendicitis
- perforation
- appendix mass
- appendix abscess --> drain
104
M:F ratio of oesophageal cancer
5:1
105
Risk factors for oesophageal cancer
Diet, excess alcohol, smoking, achalasia, obesity, low vitamin A and vitamin C, nitrosamine exposure, reflux oesophagitis
106
Sites of oesophageal cancer
- 20% = upper part
- 50% = middle
- 30% = lower
- May be squamous cell (proximal) or adenocarcinomas (distal)
107
Clinical presentation of oesophageal cancer
- Dysphagia --> progressive (initially solids, then liquids)
- Weight loss
- Retrosternal chest pain
- Upper 1/3 of oesophagus = hoarseness and cough
108
Differential diagnosis of oesophageal cancer
Oesophagitis, diffuse oesophageal spasm, achalasia, benign oesophageal stricture
109
DT for oesophageal cancer
- Oesophagoscopy with biopsy (and endoscopic ultrasound)
| - CT/MRI for staging
110
TNM staging system
- TNM system = tumour, node, metastasis
- 1-4 system =
o 1 = cancer is small
o Tumour is growing but hasn’t spread to surrounding tissues
o Cancer may have spread to lymph nodes
o Metastases
- T1 = invading lamina propria/submucosa
- T2 = invading muscularis propria
- T3 = invading adventitia
- T4 = invasion of adjacent structures
- N0 = no nodal spread
- N1 = regional node metastases
- M0 = no distant spread
- M1 = distal metastases
111
Oesophageal cancer treatment
- Poor survival rate
- Localised T1/T2 disease = radical curative oesophagestomy
- Pre-op chemo = cisplatin
- Chemotherapy
- Palliation aims to restore swallowing with chemoradiotherapy, stenting and laser use
112
M:F ratio for stomach cancer
2:1
113
stomach cancer associations
Pernicious anaemia, blood group A, H. pylori, atrophic gastritis, lower social class, smoking, nitrosamine exposure
114
Pathology of gastric cancer
- tumours mostly occur in gastric antrum
- Almost always adenocarcinomas
- Borrmann classification =
o Polyploid
o Excavating
o Ulcerating and raised
o Diffusely infiltrative
- Some are confined to mucosa and submucosa – ‘early’ gastric carcinoma
115
Symptoms of gastric cancer
often non-specific, indigestions (dyspepsia), weight loss, vomiting, dysphagia
116
Signs suggesting incurable gastric cancer
Epigastric mass, hepatomegaly, jaundice, ascites, large left supraclavicular (Virchow’s) node, Acanthosis nigricans (black hyperpigmentation of skin usually on folds)
117
Gastric cancer spread
local, lymphatic, blood-borne, trans-coelemic
118
Diagnostic tests in gastric cancer
- Gastroscopy and multiple ulcer edge biopsies
- Endoscopic ultrasound
- CT/MRI for staging
119
Treatment of gastric cancer
- Partial gastrectomy for distal tumours
- Total gastrectomy if more proximal
- Combination chemo – Epirubicin, cisplatin, 5-fluorouracil
- Surgical palliation --> for obstruction, pain or haemorrhage - 5yr survival = <10% overall
120
Small intestine tumours
rare - present with abdominal pain, diarrhoea, anorexia and anaemia
121
Treatment of malignant small bowel tumours
surgical excision or chemo/radiotherapy
122
What is a colorectal polyp?
overgrowth of epithelial cells - project into GI lumen. Normally asymptomatic but some can become malignant
123
Adenomatous polyp
most common colon polyp
Forms due to mutation in APC gene (tumour suppressor gene)
124
Histological classification of polyps
- tubular
| - villous --> become malignant
125
Pedunculated and sessile classification of polyps
- pedunculated = attached to colon by stalk
| - sessile = firmly attached to colon --> become malignant
126
Risk factors for colon polyps
- genetic conditions (familial adenomatous polyposis FAP)
- injury to bowel wall - smoking, IBD
- old age
127
Complications of polyps
- polyp ulceration --> rectal bleeding --> anaemia
| - bowel obstruction --> abdominal pain and constipation
128
Diagnosis of polyps
endoscopy and biopsy
129
Treatment of polyps
polypectomy
130
What is CRC?
most common cancer of GI tract.
| most CRCs = adenocarcinomas
131
Aetiology of CRC
- most are due to sporadic mutations
| - some are due to known mutations - polyps
132
Risk factors for CRC
- non-modifiable = old age, IBD
| - modifiable = smoking, low fibre diet, eating lots of red meat, obesity, high alcohol intake
133
Distribution of CRC
- 27% = rectum
- 20% = sigmoid colon
- 14% = caecum
134
CP of CRC in descending colon
- infiltrating masses - ring shaped --> transmural --> bowel obstruction
- altered bowel habit or obstruction
- PR mass, tenesmus
135
CP of CRC in ascending colon
- grow outwards --> vague abdominal pain and weight loss
| - can ulcerate and bleed --> iron deficiency
136
Urgent referral criteria in CRC
- Over 40 with PR bleeding and bowel habit change
- Any age with right lower abdominal pain
- Palpable rectal mass
- Men/non-menstruating women with unexplained iron deficiency anaemia
137
Diagnostic tests in CRC
Diagnostic tests
- FBC – microcytic anaemia
- Faecal occult blood – used for UK screening programme
- Sigmoidoscopy
- Barium enema or colonoscopy or CT
- Liver US/MRI
- DNA test if family history of FAP
138
Spread of CRC
- local
- lymphatic
- blood (liver, lung, bone)
- trans-coelomic
139
Dukes' criteria
o A = limited to muscularis mucosae (93%)
o B = extension through muscularis mucosae (77%)
o C = involvement of regional lymph nodes (48%)
o D = distant metastases (6.6%)
140
Treatment of CRC
- Depends on stage
o Early --> surgical resection
o Lymph node involvement --> chemotherapy
o Metastatic --> incurable – palliation = radiotherapy
141
What is a diverticulum?
A diverticulum is an outpouching of colonic mucosa that has herniated through the circular muscular layer of the large bowel at weak sites = entry of perforating arteries
142
Difference between a diverticula and diverticulosis
- Diverticula = multiple outpouchings
| - Diverticulosis = many diverticula are present with no symptoms
143
Types of diverticulum
- True = congenital --> all layers of colonic mucosa are involved in the outpouching
- False = acquired --> only mucosa and submucosa is involved
144
Risk factors for diverticulum
age, male gender, obesity, corticosteroids, exercise, NSAIDs, smoking
145
Aetiology of diverticulum
a diet low in fibre and high in meat is the strongest risk factor
146
Pathophysiology of diverticulum
- Most occur at sigmoid colon
- Firm stools require higher intraluminal pressures to propel them through the colon
- High intraluminal pressures force pouches of colonic mucosa to herniate through the muscle layers at weak points adjacent to penetrating blood vessels
147
Clinical presentation of diverticulum
- Most are asymptomatic
- Symptoms result from luminal narrowing --> pain and constipation
- Bleeding
148
Diagnostic tests for diverticulum
- Common incidental finding at colonoscopy
- Barium enema
- CT – best way to confirm acute diverticulitis
149
Complications of diverticulum
- altered bowel habit with left-sided colic relieved by defecation
- nausea and flatulence
150
Treatment of diverticula
- high fibre diet
| - anti-spasmodics - mebeverine
151
What is diverticulitis?
inflammation of the diverticula - occurs when faeces obstruc the neck of the diverticulum
152
CP of diverticulitis
```
LIF pain
fever
nausea
pyrexia
raised WCC
tender colon
localised/generalised peritonitis
```
153
DT for diverticulitis
barium enema, CT,
| FBC - raised CRP/ESR
154
Treatment of diverticulitis
- analgesia, nil by mouth, IV fluids, CT-guided percutaneous drainage (if abscess)
- surgical - colectomy (indicated in perforation and fistula)
155
Complications of diverticulitis
- perforation --> abscess formation or peritonitis
- fistula formation into bladder or vagina
- intestinal obstruction
