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Pathology Term 2 > Week 6 - LOWER GIT > Flashcards

Week 6 - LOWER GIT Flashcards

IBD, Polyps, Colon Cancer, Malabsorption, Haemorrhoids

1
Q

What are the 3 supposed etiological factors for IBD?

A

*unkown etiology

  1. genetic susceptibility –> HLA-DR1/DR7
  2. environmental factor –> gut flora
  3. immune dysfunction –> autoimmunity
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2
Q

True or False?

IBD increased risk in western countries

A

True

-hygiene theory?

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3
Q

True or False?

Smoking decreases risk and severity of chron’s disease but increases risk/severity of ulcerative colitis

A

False

-other way around

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4
Q

What 2 inflammatory mediators play a role in the development of IBD?

A
  1. TNF-alpha
    - T cell over activation (increased inflamm.)
  2. IL-10
    - mutations of IL-10 and its receptor genes –> severe/early onset IBD –> decreased anti-inflammatory effect
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5
Q

What is the new drug of promise for IBD?

A

Anti-TNF alpha antibody

e.g. remicade/infliximab

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6
Q

What is the pathogenesis of IBD?

A
  1. excess TNF-alpha
  2. decreased IL-10 (IL-10 normally STOPS inflamm.)
  3. UNCONTROLLED INFLAMMATION
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7
Q

Compare CD and UC, and what % is Inderterminate Colitis?

A

CD:

  • whole GIT
  • patchy “skip lesions”
  • thick, narrow, deep ulcers - transmural
  • chronic granuloma
  • ulcerations/fissures
  • fibrous

UC:

  • colon mucosa ONLY (not serosa)
  • continuous, thin, dilated
  • acute inflammation
  • ulcers/pseudopolyps
  • broad, shallow ulcers
  • NO thickening, fibrosis, narrowing or granulomas

*10% cases = indeterminate colitis (mixed pattern)

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8
Q

Where can CD affect and where does it most commonly affect?

A
  • ANYWHERE in the GIT (mouth –> anus)

- commonly affects cecum + terminal ileum (RLQ)

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9
Q

What are the gross features of CD?

A
  1. mucosa –> “cobblestone” (narrow deep ulcer)
  2. wall –> thick + fibrotic
  3. skip lesions (patchy)
  4. creeping mesenteric fat (as inflammation spreads to the serosa)
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10
Q

What is ‘string sign’?

A

radiographical sign on CD whereby narrow crohn’s segments DO NOT take up the contrast/dye

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11
Q

What are microscopic features of CD?

A
  • narrow deep ulcers
  • transmural inflammation
  • lymphocytes
  • granuloma ( lymphocytes, macrophages, giant cells, NO caseation)
  • crypt abscess (also in UC) –> WBCs accumulate within crypts
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12
Q

True or False?

Skip lesions present in both CD and UC

A

False

- only in CD

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13
Q

What are the features + complications of CD?

A
  • spreading, granulomatous inflammation
  • fibrosis
  • thickening
  • narrowing
  • obstruction
  • adhesions
  • fistula/sinus –> watering pot perineum
  • abscess
  • anemia (iron/B12)
  • adenocarcinoma
  • malabsorption synd.
  • polyarthritis
  • erythema nodosum/pyoderma granulosum
  • apthous ulcers
  • scleritis
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14
Q

When does UC affect the ileum?

A

“backwash ileitis”

-when whole of colon is affected, inflammatory mediators can enter ileum causing ileitis (inflamm.) –> but NO ulcer formation

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15
Q

True or False?

inflamm. in UC is limited to mucosa

A

True

-serosa is normal (unlike in CD)

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16
Q

What is toxic megacolon?

A
  • total paralysis and loss of peristalsis of colon due to toxic damage to muscular layer
  • dilated, stasis, gangrene
  • complication of UC
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17
Q

Why is the active disease of UC in the right side of the colon?

A
  • UC begins in the rectum and gradually spreads from L –> R colon
  • therefore L side becomes atrophic with atrophic mucosa and smooth sides (inactive UC phase) and R side becomes active (red/granular)
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18
Q

What is a pseudopolyp?

A
  • complication of UC

- oedematous, intact area of mucosa between broad/shallow ulcers

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19
Q

What are the gross and microscopic features of UC?

A

Gross:

  • ulcers (broad/shallow)
  • pseudopolyps

Micro:

  • acute inflammation limited to mucosa
  • crypt abcsess (WBCs inside glands)
  • pseudopolyps
  • NO granuloma
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20
Q

What 2 key complications can occur in UC but not in CD?

A
  1. toxic megacolon
  2. perforation

N.B. Haemorrhage risk markedly increased in UC compared to CD

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21
Q

Which IBD is colonic cancer more likely to occur in?

A

UC - pancolitis

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22
Q

Which IBD has an increased risk of developing malabsorption syndrome and why?

A

CD

  • involves ileum –> impaired fat metabolism/B12 absorption –> malabsorption
  • UC only affects colon
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23
Q

Which macrophage activation pathway is seen in UC and CD?

A

UC –> M1 (increased inflamm. + NO fibrosis)

CD –> M2 (significant fibrosis + granulomatous inflamm.)

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24
Q

What are the types of polyps?

A
  1. non-neoplastic (90%)
    - low/no malignancy
    - hyperplastic –> most common
    - inflammatory/pseudopolyps –> IBD
    - hamartoma/congenital/juvenile polyps
  2. neoplastic (10%) adenoma
    - high malignancy (oncogene activation)
    - tubular (90%), tubulovillous (10%), villous (1%)
    - sporadic/familial (FAP, HNPCC)
    - adenocarcinoma
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25
What are the features of hyperplastic polyps?
- commonest --> non-neoplastic - small (<5mm) - distal/L side - sigmoid colon - sessile, multiple, normal colour Micro: - increase large glands - hyperplasia - NO dysplasia (normal function)
26
What neoplastic polyp is similar in appearance to hyperplastic polyps?
Sessile Serrated Adenoma - neoplastic - R side (cecum)
27
Clinically, what is the commonest polyp seen?
hyperplastic polyp
28
What type of congenital polyps are present in children <3yrs and in adults?
<3yrs -juvenile polyps (rectum) adults -retention polyps *congenital hamartomas
29
What are the 2 types of juvenile polyposis syndromes?
1. Peutz-Jeghers Syndrome - STK11 (tum. spp. gene) - SI, stomach, colon - oral pigment macules --> brown/black ulcers in mouth 2. Cowden Syndrome - PTEN (tum. spp. gene) - GI polyps with lipomas, neuromas, etc - GI malignancy
30
How many polyps are seen in familial adenomatous polyposis (FAP) and what gene mutation causes it?
- 100 - 2500 - APC gene mutation (autosomal dominant) - 100% pts. will get adenocarcinoma <50yrs
31
What is HNPCC also referred to as?
Lynch syndrome
32
How many polyps are present in HNPCC and what genes are mutated?
- none or <100 polyps - MSH2 or MLH1 (DNA repair genes) - malignancy later age than FAP (still younger than sporadic colon cancer)
33
What is the commonest neoplastic polyp type?
tubular adenoma (90%)
34
Describe gross appearance of tubular vs. villous adenomas?
Tubular -like a 'fruit' hanging from a stalk (pedunculated) Villous -like a 'carpet' of multiple villous structures
35
What is the commonest carcinoma of the colon?
adenocarcinoma
36
What % of colon cancer is sporadic and what is the peak age group? What % is familial?
- 80% sporadic (peak 60-70yrs) | - 20% familial (<50yrs)
37
What is the most popular population screening method for colon cancer?
Stool Occult Blood | -in >50y.o.
38
What are the 2 types of colon cancer?
1. Right/Proximal/Familial | 2. Left/Distal/Sporadic
39
Why is it supposed aspirin has a protective effect on colon cancer?
- aspirin inhibits COX2 | - colon cancer expresses increased levels of COX2
40
What are the 2 main etiological factors for colon cancer?
1. Environmental - decreased dietary fibre + increased refined fat/carbohydrates --> increased anaerobic bacteria --> increased cholesterol --> increased risk - aspirin, calcium, folates --> PROTECTIVE 2. Genetic - APC/B-catenin --> tumour spp. genes (80%) - MLH1/MSH2 --> DNA repair + TGF-B genes (20%) - other genes: - BAX, KRAS, TP53, etc.
41
What are the 2 pathogenetic pathways for colon carcinoma?
1. More common 80% - germline/somatic mutations of tum. spp. gene (APC) --> first hit - inactivation of normal allele (risk factors) --> second hit - overexpression of COX2 --> adenomas (dysplasia) --> carcinomas 2. DNA mismatch repair pathway 20% - MLH1/MSH2 --> HNPCC - microsatellite instability --> microadenomas --> carcinomas (NO polyps)
42
What is the commonest clinical feature of colon cancer?
ASYMPTOMATIC - fatigue (IDA) - wt. loss, etc. (normal malig. features)
43
What are the clinical features of L + R sided colon cancer?
Left: - distal/rectal tumours may be palpable on P/E - colicky lower abdo. pain --> constricting/early obstruction - diarrhoea, bleeding --> fresh blood - sporadic increased Right: - anemia/wt. loss - polypoid - NO obstruction - occult bleeding --> requires lab tests - familial increased
44
What are some rare complications of colon cancer?
- perforation - peritonitis - abscess - fistula
45
Which side colon cancer is referred to as 'napkin ring'/apple core?
Left-sided: - constricting --> obstruction - fresh blood in stools - distal colon - sporadic common - CONSTIPATION
46
What are the microscopic features of adenocarcinoma of the colon?
irregular, pleomorphic cells forming irregular glands (with necrosis)
47
Outline Dukes staging for colon cancer? and clinically, when is the Dx. most likely to be made at?
A --> tumour confined within bowel wall B --> extension through bowel wall (no LN involvement) C --> tumour involving LN's D --> distant metastasis *B/C --> 65% of diagnoses made here
48
True or False? | familial cancers commonly located on L side
False | - right side
49
Why can you get mixture carcinomas in anal canal?
- comprised of 3 different types of epithelium * deep --> superficial: 1. columnar - adeno. 2. transitional - mixed (basaloid squamous carcinoma) 3. squamous - squamous
50
Where do basaloid squamous carcinomas occur and describe features?
- rectum/anal canal (transitional epithelium) - basal cell carcinoma (i.e. skin) - basaloid cells around tumour (palisading "fence-like") - keratin pearls + mucin may be present - locally invasive (no metastasis)
51
What is the definition of diarrhoea and what are the causes/
- increase in stool mass (>200g/day), frequency or fluidity volumes (>200mL/day) causes: - infection, inflammation, ischaemia, malabsorption + nutrition
52
What are the types of diarrhoea?
1. secretory - excess intestinal secretion - isotonic stool persists during fasting - bile/pancreatic disorders 2. osmotic - unabsorbed luminal solutes - lactase deficiency 3. malabsorptive - fat, pale, greasy stools --> relieved by fasting 4. exudative - inflamm/infection - purulent, bloody --> continues during fasting - IBD
53
What are the 3 main causes of malabsorption disorders?
1. Secretory defects --> bile, pancrease 2. Motility/bacteria --> DM, infections 3. Mucosal damage --> sprue, whipple
54
What are the clinical features of malabsorption disorders?
- chronic diarrhoea (decreased absorption) - wt. loss, anorexia, bloating --> due to fermentation of nutrients causing increased CO2 - steatorrhoea --> pale, greasy stools - Vit D (hypocalcemia) + Vit K (bleeding) deficiencies - ADEK --> fat-soluble vitamins decreased due to decreased FAT absorption
55
What vitamins are deficient in malabsorption disorders and why?
ADEK --> fat-soluble vitamins | -due to decreased fat absorption in malabsorption syndromes
56
What % of bile acids are actively reabsorbed and where does this occur?
95% in terminal ileum and recycled through enterohepatic cycle 6-8x/day
57
What alleles are affected in celiac disease and what autoantibodies do celiacs possess?
- HLA-DQ2 or DQ8 | - IgA antigliadin Ab/IgA transglutaminase Ab --> JEJUNUM
58
What is the pathogenesis of celiac disease?
- immune enteropathy to protein gluten (gliadin fraction) - genetic predisposition --> HLA DQ2/DQ8 + IgA antigliadin Ab --> cross-reacts with jejunal mucosa brush border --> inflammatory/immune-mediated damage of jejunal mucosa --> decreased SA --> decreased absorption (VILLOUS ATROPHY = DECREASED ABSORPTIVE CAPACITY)
59
What is the pathogenesis of tropical sprue/ environmental enteropathy?
1. poor hygiene/sanitation 2. feco-oral infections 3. intestinal inflammation 4. immune activation 5. environmental enteropathy 6. malabsorption 7. malnutration --> back to 1.
60
What is autoimmune enteropathy?
IPEX - Immune dysregulation Poly-Endocrinpathy + X-linkage - severe diarrhoea in young children
61
What is the pathogenesis of lactose intolerance?
lactase deficiency --> increased lactose --> osmotic diarrhoea --> lactose fermented by bacteria (increased CO2 --> gas + cramps)
62
What is seen on microscopy of Whipple's disease?
- plenty of foamy macrophages in mucosa, full of partly digested rod-shaped bacilli --> Tropheryma whippelii (gram + actinomycete) - PAS stain +, little/no inflamm.
63
True or False? | Malabsorption in Whipple's is due to lymphatic block
True
64
What are haemorrhoids and what are typical causes?
- dilatation of veins due to increased haemorrhoidal venous pressure causes: - straining, constipation, pregnancy, portal HTN
65
What are the 2 types of haemorrhoids?
1. External - inferior plexus - below anorectal line 2. Internal - superior plexus - above anorectal line
66
What are the clinical features and Tx. of haemorrhoids?
CF's: - >30yrs - pain, mass, bleeding - bright red blood on toilet paper Tx. - scleropathy - band ligation - IR coag. - surgery

Pathology Term 2 (6 decks)

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