Pathology -- Autoimmune Diseases Flashcards
1
Q
Define MALT
A
Mucosa Associated Lymphoid Tissue = a specialized immune system which protects mucosal surfaces (i.e. GIT, bronchial tree, nasopharynx, GU tract)
2
Q
Role of MALT in the GIT
A
- Absorption of nutrients
- Need and effective barrier and a selective response (innate and acquired immune system) to various substances (harmless vs. harmful)
3
Q
What constitutes an effective barrier in the mucosal immune system
A
Intact intestinal epithelium (surface mucosa, peristalsis, protective secretory factors)
4
Q
Define the innate immune system
A
Initial response to antigen exposure (neutrophils, macrophages, NKCs)
5
Q
Define the adaptive immune system
A
Specific immuntiy to antigens (APCs with molecules of the major histocompatibility complex) = self from non-self
i.e. B and T lymphocytes, dendritic cells
6
Q
One hypothetical equation to explain the cause of IBD
A
7
Q
5 risk factors for IBD
A
- Age = young
- Ethnicity = Causacians (particularly Ashkenazi Jews)
- Family history
- Geography = US and Europe
- Smoking
8
Q
Incidence of IBD
A
CD = 16.9 per 100,000
UC = 12.9 per 100,000
9
Q
Provinces with the highest incidence of IBD
A
QC and NS
10
Q
Prevalence of IBD in Canada
A
0.7% (233,000)
11
Q
Describe the role of family history in the risk of developing IBD
A
1st degree relative = 12 - 25% risk
Monozygotic twins = 60% concordance
12
Q
Describe the role of smoking in the risk of developing IBD
A
Active smokers are more than 2 times as likely to develop CD than nonsmokers, but less likely to develop UC (smoking is actually protective??)
13
Q
How is IBD diagnosed?
A
Clinical diagnoses relying on:
- Clinical history (symptoms)
- Laboratory findings
- Endoscopic features
- Histological evaluation
- Radiographic evaluation
- Rulling out infectious etiologies
14
Q
4 lab tests for IBD
A
- Tests for anemia
- B12 deficiency
- Increased CRP
- Fecal calprotectin
15
Q
3 endoscopic methods for diagnosing IBD
A
- Gastroscopy
- Colonoscopy
- Capsule endoscopy
16
Q
3 radiographic evaluation tools for diagnosing IBD
A
SBFT or CT or MR enterography
17
Q
2 subsets of IBD
A
Crohn’s disease
Ulcerative colitis
18
Q
7 characteristics of Crohn’s disease
A
- Chronic inflammatory disease
- Affects any segment of the luminal GIT (mouth -> anus)
- Transmural involvement
- Rectum usually spared
- Sharply delineated areas affected with intervening normal bowel (“skip areas”)
- Noncaseating granulomas
- Fistulization
19
Q
Describe the anatomical distribution of CD
A
20
Q
4 clinical patterns of CD
A
+ Fistulae and abscesses
21
Q
2 general clinical features of CD
A
- Intermittent diarrhea and abdominal pain
- GI bleeding
22
Q
3 chronic clinical features of CD
A
- Strictures
- Fistulas
- Malabsorption
23
Q
7 morphological features of CD
A
- Mucosal erythema/edema
- Superficial ulcers
- Deep linear ulcers on axis
- Nodularity from skip areas (cobblestoning)
- Bowel wall thickens, lumen narrows (string sign)
- Edematous mesentery (creeping fat)
- Extension of fissuring (fistulae, abscesses, adhesions, perforations)
24
Q
5 histologic features of CD
A
- Mucosal inflammation
- Chronic mucosal damage
- Ulceration (abrupt)
- Transmural inflammation
- Granulomas (10 - 30%)
- Thickening/fibrosis
25
Describe the mucosal inflammation of CD
Crypt abscesses
26
3 features of chronic mucosal damage seen histologically in CD
* Glandular distortion
* Pyloric metaplasia
* Paneth cell metaplasia
27
How does CD progress anatomically over time?
Location remains stable over time (note that 1/3 have penetrating/stricturing complications)
28
How common is prolonged remission in CD
Only 10% within 10 years
29
4 complications of CD
* Annual incidence of hospitalization = 20%
* Steroid dependency = 33%
* Surgery post diagnosis = 50% within 10 years
* Post-operative recurrence = 50% within 10 years
30
7 characteristics of UC
* Chronic inflammatory disease
* Affects the colorectum (may be whole colon = pancolitis)
* Generally restricted to the mucosa
* Rectal involvement
* Contiguous to varying extent
* 10% with "backwash ileitis"
* No granulomas
31
Describe the therapy for CD
Top down therapy:
32
Describe the anatomic distribution of UC
33
Describe the clinical features of UC
A spectrum of effects based on disease progression where:
* Proctitis = mild
* Left-sided colitis = moderate
* Pancolitis = severe
34
5 mild clinical features of UC
* Intermittent bleeding
* Fewer stools daily
* Mucous
* Tenesmus
* Constipation
35
3 moderate clinical features of UC
* More bleeding
* More daily stools
* Left-sided cramps
36
5 severe clinical features of UC
* Significant bleeding
* Frequent stools
* Increasing pain
* Fevers
* Megacolon
37
When can toxic megacolon occur?
* Most severe cases of UC
* Corhn's colitis
38
Define toxic megacolon
Toxic damage to muscularis propria and neural plexus, negatively affecting neuromuscular function --\> colon dilates and becomes gangrenous
39
4 morphologic features of UC
* Mucosal erythema, granularity, friability
* Broad ulceration (on axis)
* Regenerating mucosa (pseudopolyps)
* Progressive mucosal atrophy (flattened surface, no mural thickening)
40
Describe the histology of UC
* Chronic mucosal changes similar to CD
* Mononuclear infiltrate
* Crypt abscesses
* Glandular distortion
* No granulomas
41
Describe the anatomical progression of UC over time
* Disease location remains stable over time
* Proximal progression in 5 - 15% over 5 years
* Distal disease = 20% resolve spontaneously
42
10 year colectomy rate for UC
9 - 21% (35% at 20)
43
2 complications of UC
* IPAA (ileal pouch anal anastomosis)
* Risk of colon cancer
44
4 characteristics of IPAA
* Pouchitis (50% within 5 years)
* Female infertility
* Nocturnal incontinence
* Pouch failure
45
What is the risk of colon cancer in UC patients?
0.3 - 0.5% per year increase after 8 - 10 years of disease
46
Describe the treatment for UC
47
Extraintestinal manifestations of IBD
* **C**holangitis (primary sclerosing cholangitis)
* **H**ematologic (anemia, hemolysis, amyloid)
* **E**ye (episcleritis, uveitis)
* **T**hromboembolism
* **S**kin (E. nodosum, pyoderma gengrenosum)
48
4 other extraintestinal manifestations of IBD unrelated to the CHEATS mnemonic
* Kidney stones
* Gallstones
* Osteomalacia
* Pericarditis
49
Define celiac disease
T-cell mediated immune disease os the small intestine triggered by gliadin (gluten protein) found in wheat, rye, and barley
50
Describe the genetic factors of celiac disease
Chromosome 6
* HLA DQ2 and DQ8 gene loci
* \>98% in celiac disease, but present in 30% of Caucasians; necessary but not sufficient for disease occurrence
51
Pathogenesis of celiac disease
1. On exposure to gliadin, tissue transglutaminase (TTG) modifies the protein
2. Immune system cross reacts with the small bowel tissue
3. Intraepithelial infiltration by CD8+ T cells
4. Mucosal inflammation, crypt hyperplasia and villous atrophy
52
5 classifications of celiac disease
* Classic or typical celiac disease
* Atypical celiac sprue
* Asymptomatic (silent) celiac disease
* Latent (potential) celiac disease
* Refractory celiac disease
53
Define classical/typical celiac disease
Gluten-sensitive enteropathy found in association with villous atrophy, malabsorption and resolution of symptoms and mucosal lesions on a gluten free diet
54
Define atypical celiac sprue
Gluten-sensitive enteropathy with only minor GI symptoms but atypical manifestations, including anemia, osteoporosis, arthritis, neurological symptoms and infertility
55
Define asymptomatic (silent) celiac disease
Gluten-sensitive enteropathy found after serological screening in asymptomatic patients
56
3 characteristic symptoms of malabsorption
* Steatorrhea
* Weight loss
* Vitamin deficiency
57
Define latent (potential) celiac disease
Patients who have normal villous architecture on a gluten-containing diet (but have serological markers positive for celiac disease)
58
Define refractory celiac
Symptomatic, severe small intestinal villous atrophy, but does not respond to at least 6 months of a strict gluten-free diet
59
Which type of celiac disease is more common?
Silent celiac sprue = 7x more common than symptomatic celiac sprue
60
Prevalence of celiac disease in North America
1:100 to 1:130
61
Genetic risk factors for celiac disease
* First degree relatives = 10 - 20% disease prevalence
* Monozygotic twins = 75% concordance
62
Mean age of presentation for celiac disease
45
63
8 clinical features of presentation for celiac disease
* Episodic diarrhea (up to 10x per day; nocturnal or early morning diarrhea is common)
* Distention
* Steatorrhea
* Flatulence
* Weight loss
* Vague abdomnal discomfort/fatigue
* Anemia
* Recurrent aphthous ulcers
64
6 extraintestinal manifestations of celiac disease
* Anemia (impaired reabsorption)
* Metabolic bone disease
* Neuropsychiatric disease
* Hyposplenism
* Kidney disease
* Dermatitis herpatiformis
65
Why might anemia accompany celiac disease?
Impaired reabsorption in the small intestine
* Proximal = iron and folate deficiency
* Ileum = B12 deficiency
66
Why might metabolic bone disease accompany celiac disease?
* Impaired calcium absorption
* Vitamin D deficiency
67
Define dermatitis herpetiformis
Pruritic papules in grouped arrangements that improve on a gluten free diet
68
How do you histologically confirm the presence of dermatitis herpetiformis?
Granular IgA deposits in the subepidermal basement membranes
69
5 serological tests that can be done to diagnose celiac disease
* IgA EMA (endomysial antibodies)
* IgA tTG (tissue transglutaminase)
* Anti IgA AGA (anti-gliadin antibodies)
* Anti-IgG AGA
* Anti-IgG tTG
70
Gold standard for diagnosing celiac disease
IgA EMA (endomysial antibodies)
71
Statistical features of the IgA EMA test
* Sensitivity = 90%
* Specificity = 99%
* Reproducibility = 93%
72
Statistical features of the IgA tTG test
* Sensitivity = 93%
* Specificity = 95%
* Reproducibility = 83%
73
Advantage of using IgA tTG as a diagnostic test for celiac disease
Cheaper and more available than IgA EMA
74
Disadvantage of using IgA tTG to diagnose celiac disease
False positives in patients with other auto-immune or liver diseases
75
What serological test can be used to assess patient compliance to a gluten-free diet for treating celiac disease?
IgA tTG (should fall to normal or "baseline" within 3 - 6 months)
76
Least reliable serological test for diagnosing celiac disease
Anti IgA AGA
77
When should Anti-IgG AGA or Anti-IgG tTG be used to diagnose celiac disease?
For patients with IgA deficiency (10% of the population)
78
4 endoscopic findings for celiac disease
* Absent folds
* Scalloping
* Mosaicism
* Fissures
79
How can celiac disease be diagnosed by biopsy?
Marsh classification by biopsying in D2 and the duodenal bulb
80
Describe the March Classification in diagnosing celiac disease
Histological definitions with 5 stages from STAGE ZERO to STAGE FOUR
81
Stage zero of the marsh classification
Preinfiltrative mucosa. Increase in IELs (not enough to diagnose celiac at this stage)
82
Stage one of the marsh classificaiton
Infiltration of the lamina propria with lymphocytes
83
Stage two of the marsh classification
Crypt hyperplasia
84
Stage three of the marsh classification
Villous atrophy
85
Stage four of the marsh classification
Total mucosal atrophy. Complete loss of villi, enhanced apoptosis, more crypt hyperplasia
86
How to treat celiac disease
Gluten free diet
87
7 advice points to follow a gluten free diet
* Avoid all foods containing wheat, rye, and barley gluten
* Avoid all oats initially (gluten contamination)
* Read all labels and study ingredients of processed foods
* Beware of gluten in medications, food additives, emulsifiers, or stabilizers
* Limit milk and milk products initially
* Avoid all beer, lagers, ales, and stouts
* Wine, liqueurs, ciders, and spirits, including whiskey and brandy are allowed
88
Why is celiac disease associated with lactose intolerance?
Loss of villi in small intestine = loss of lactase found on the lining = inability to digest lactose
89
Complications of uncontrolled celiac disease
Malignancy (2.6 - 3.1 fold increase risk)
* Lymphoma (2/3)
* Oropharynz, esophagus, and small intestine malignancies (1/3)
Ulcerative jejunoileitis
90
How can someone reduce their risk for malignancies if they have celiac disease
Risk is reduced to normal after 5 years of gluten-free diet
91
Specific lymphoma associated with celiac disease
EATL = enteropathy associated T cell lymphoma
92
Problem with EATL
Difficult to diagnose and fatal
93
When can EATL occur?
After 20 - 30 years of having uncontrolled celiac disease
