Alimentary Tract Pathology Flashcards
what is the role of the small bowel?
absorption
what is the role of the large bowel?
absorption and secretion
how long is the small intestine?
6m long
what is the small bowel divided into?
Divided into –duodenum 1st 25cm and is retroperitoneal
Jejunum
Remainder ileum
what is the large bowel divided into?
Caecum
Ascending colon-retroperitoneal
Transverse colon
Descending colon-retroperitoneal
Sigmoid –originates pelvic brim
Rectum-15cm, distal 7cm
extraperitonea
what are the three cell types found in small bowel?
goblet cells
columnar absorptive cells
endocrine cells
where are crypts located histologically?
base of the villi
what is contained within the crypts?
stem cells
goblet cells
endocrine cells
paneth cells
what are paneth cells?
Paneth cells are secretory cells located in the crypts of Lieberkühn, adjacent to the intestinal stem cells. They produce antimicrobial peptides and proteins and other components that are important in host defense and immunity
what are the layers of the small bowel going from the superficial lamina propria?
muscularis mucosa, submucosa
muscularis propria and subserosa
how often are the epithelial cells and lining of the
lumen renewed in the small bowel?
every 4-6 days
describe histologically the surface of the large bowel
Flat –no villi
Tubular crypts
Surface-columnar absorptive cells
Crypts-goblet cells, endocrine cells
how often are the epithelial cells and lining of the
lumen renewed in the large bowel?
every 3-8 days
what is presented by the GI tract for exposure by environmental antigens?
large surface area
what must the immune system of the GI tract do?
must balance the tolerance of harmless ingested substances against active defense reactions to potential microbial invaders.
what would dysfunction of the GI tract result in?
Chronic Disease
Life threatening acute conditions
what is the peristalsis of both the small and large bowel mediated by?
intrinsic (myenteric plexus) and extrinsic (autonomic innervation) neural control
what is the myenteric plexus?
The myenteric plexus, also known as Auerbach’s plexus, is located between the longitudinal and circular muscle layers of the esophagus, stomach, and small and large intestine.
The myenteric plexus is principally responsible for the peristaltic movement of the bowels. While it can act independently from the central nervous system, it receives innervation from the autonomic nervous system, connecting the central and enteric nervous systems.
What is the myenteric plexus formed from?
meissener’s plexus (base of submucosa)
Auerbach plexus (between the inner circular and outer longitudinal layers of the muscularis propria)
Auerbach plexus
between the inner circular and outer longitudinal layers of the muscularis propria
Meissener’s plexus
base of the submucosa
what are two pathologies of the lower GI tract?
Inflammatory Bowel Disease
Large Bowel Neoplasia
what are the pathological features of inflammatory bowel disease?
Ulcerative colitis
Crohn’s disease
Ischaemic colitis
Radiation colitis
Appendicitis
what is idiopathic inflammatory bowel disease?
Chronic inflammatory conditions resulting from inappropriate and persistent activation of the mucosal immune system driven by the presence of normal intraluminal flora
what are the 2 main diseases that make up idiopathic inflammatory disease?
Crohn’s disease
Ulcerative colitis
how would you compare crohns disease and ulcerative colitis?
Many common features but have distinctly different clinical manifestations
which parts of the body does crohns disease affect?
CD can affect any part of the GIT from the mouth to the anus
which parts of the body does ulcerative colitis affect?
limited to colon
Do Crohn’s disease and ulcerative colitis have extra-intestinal manifestations?
Yes both do
Idiopathic inflammatory bowel disease aetiology
Strong immune response against normal flora with defects in the epithelial barrier function in genetically susceptible individuals
What is the genetic pathogenesis of idiopathic inflammatory bowel disease?
Genetics-15% have affected 1st degree relatives
Lifetime risk of 9% if either a parent or sibling is affected
What gene mutation is associated with Crohn’s disease?
NOD2 gene mutation
What gene mutation is associated with ulcerative colitis?
HLA
What is the role of intestinal flora?
Specific microbe not yet identified
Defects in mucosal barrier could allow microbes access to lymphoid tissue triggering immune response
IBD - exaggerated immune response
What does the diagnosis of IBD require?
Requires clinical history, radio graphic examination and pathological correlation
What antibody is positive in 75% of UC patients but only 11% CD patients
pANCA
Does ulcerative colitis affect males or females more prominently?
Both males and females equally
What are the two age groups most affected by ulcerative colitis?
20-30 years
70-80 years
What is the affected location of ulcerative colitis?
Can be localised to the rectum
More commonly spreads proximally
What associations with other organs and conditions can ulcerative colitis have?
10% pancolitis
Appendix
Systemic manifestations
Is the large bowel or small bowls involved with ulcerative colitis?
Large bowel
Describe the pathology of UC
Continuous pattern of inflammation
Rectum to proximal
Pseudopolyps
Ulceration
Serosal surface minimal or no inflammation
Describe the histology of ulcerative colitis
Mucosa inflammation
Crypt abscesses
Architectural disarray of crypts
Mucosal atrophy
Ulceration into submucosa-pseudopolyps
Limited mainly to mucosa and sub mucosa
No granulomas
Sub mucosal fibrosis
What features of dysplasia are shown in ulcerative colitis?
Reactive atypia/dysplasia
Dysplasia is either high or low grade
Flat epithelial atypia —> adenomatous change —> invasive cancer
Risk if pancolitis> 10 years 20-30 times higher risk of developing cancer
What are other complications from ulcerative colitis
Haemorrhage
Perforation
Toxic dilatation
What is the role of intetinal flora for IBD?
Specific microbe not yet identified
Defects in mucosal barrier could allow microbes access to mucosal lymphoid tissue triggering immune response
How is IBD diagnosed?
Requires clinical history, radiographic examination and pathological correlation
What is pANCA?
Perinuclear antineutrophilic cytoplasmic antibody
How does pANCA differ between Crohn’s and ulcerative colitis?
Postive in 75% of ulcerative colitis
Positive in 11% of Crohn’s disease
How does the incidence of ulcerative colitis change between males and females?
Affected equally
What age groups does ulcerative colitis peak?
20-30 years and 70-80 years
What is ulcerative colitis that is localised to the rectum called?
Proctitis
Where is ulcerative colitis more commonly spread?
Proximally
Can the appendix be involved in ulcerative colitis?
Yes
What is the pathology of ulcerative colitis?
affects the large bowel only
has a continuous pattern of inflammation
inflammation rectum to proximal
signs of pseudo polyps, ulceration, serosal surface has minimal to no inflammation
What are pseudopolyps?
markers of episodes of severe inflammation, encountered in endoscopy in a subgroup of patients with ulcerative colitis (UC) Their clinical significance is uncertain, except for their link with an intermediate risk for colorectal cancer.
in UC is there inflammation of the serial surface?
no, there is minimal to no inflammation
what does ulcerative colitis histology show?
Mucosa – inflammation
Cryptitis
Crypt abscesses
Architectural dissarray of crypts
Mucosal atrophy
Ulceration into submucosa- pseudopolyps
Limited mainly to mucosa and submucosa
NO granulomas.
Submucosal fibrosis
Where is inflammation due to ulcerative colitis limited to in the gut wall?
mainly to mucosa and submucosa
Are granulomas present in ulcerative colitis?
no
What is a granuloma?
A granuloma is a tiny cluster of white blood cells and other tissue. It can appear in your lungs, skin or other parts of your body. Granulomas aren’t cancerous. They form as a reaction to infections, inflammation, irritants or foreign objects.
What is granulation tissue?
Granulation tissue is new connective tissue and microscopic blood vessels that form on the surfaces of a wound during the healing process.
What is a form of ulcerative colitis that affects the entire bowel?
pan colitis
How does having pancolitis for more than 10 years change the risk for developing cancer?
20-30 x higher risk of developing cancer.
What are some complications of ulcerative colitis?
Haemorrhage
Perforation
Toxic dilatation
Where in the GIT can Crohn’s disease affect?
Any level of GIT from mouth to anus
Is the incidence of Crohn’s disease increasing or decreasing?
increasing
who is more commonly affected by Crohns disease?
Females > males
Any age including childhood
More common in Caucasians 2-5x
3-5x more common in the Jewish population.
40% SI, 30% SI and LI , 30% Colon
what age groups are more commonly affected by crohns disease?
Peaks 20-30 years and also 60-70 years
What is the pathology of Crohn’s disease?
Granular serosa / dull grey
Wrapping mesenteric fat
Mesentry- thickened, oedematous and fibrotic
Wall thick, oedematous
Narrowing of lumen
Sharp demarcation of disease segments from adjacent normal tissue “skip lesions”
Ulceration- “cobblestone”
What can be seen in Crohn’s disease histology?
Cryptitis and crypt abscesses
Architectural distortion
Atrophy –crypt destruction
Ulceration-deep
Transmural inflammation
Chain of pearls
Non-caseating granulomas
Fibrosis
Lymphangiectasia
Hypertrophy of mural nerves
Paneth cell metaplasia
What is inflammation of an intestinal crypt called?
Cryptitis
What are long term features of Crohn’s disease?
SI – malabsorption
Strictures
Fistulas and abscesses
Perforation
How does Crohn’s disease change the risk of developing cancer?
Increased risk of cancer - 5x increased risk over the same age matched population.
What are the macroscopic differences between Crohn’s disease and ulcerative colitis?
CD
colon and ileum
skip lesions
variable strictures
thickened wall appearance
UC
colon only
diffuse distribution
late, rare stricture
thin wall appearance
What are the microscopic differences between Crohn’s disease and ulcerative colitis?
CD
transmural inflammation
marked pseudopolyps
deep linear ulcers
marked lymphoid reaction
moderate fibrosis
variable serositis
granulomas
fistulae/sinuses
UC
limited to mucosa
marked pseudopolyps
superficial ulcers
mild lymphoid reaction
mild fibrosis
mild to no serotitis
no granulomas
no fistulae/sinuses
What is ischaemic enteritis?
Ischemic colitis occurs when blood flow to part of the large intestine is temporarily reduced
Ischaemic lesions can be restricted to either the SI or LI or they can affect both depending on vessel affected
Where are ischaemic lesions found in ischaemic enteritis?
Ischaemic lesions can be restricted to either the SI or LI or they can affect both depending on vessel affected
What does acute occlusion of one of the 3 major supply vessels lead to?
infarction (Coeliac, Inferior and Superior mesenteric arteries)
What is infarction?
obstruction of the blood supply to an organ or region of tissue, typically by a thrombus or embolus, causing local death of the tissue.
Is mesenteric venous or arterial occlusion more common?
Mesenteric venous occlusion less common
Why does gradual occlusion of intestinal blood supply have little effect?
anastomotic circulation
What are some predisposing conditions for ischaemic enteritis?
Arterial thrombosis
severe atherosclerosis
systemic vasculitis eg PAN,HSP,WG
dissecting aneurysm
hypercoagulable states
oral contraceptives
Arterial embolism
cardiac vegetations
acute atheroembolism
cholesterol embolism
Non-occlusive ischaemia
cardiac failure
shock /dehydration
vasoconstricive drugs eg propanolol
What can cause arterial thrombosis?
severe atherosclerosis
systemic vasculitis eg PAN,HSP,WG
dissecting aneurysm
hypercoagulable states
oral contraceptives
What can cause arterial embolism?
cardiac vegetations
acute atheroembolism
cholesterol embolism
What can cause non-occlusive ischaemia?
cardiac failure
shock /dehydration
vasoconstricive drugs eg propanolol
What part of the colon is most vulnerable to acute ischaemia?
Splenic flexure vulnerable
what is caused by acute ischaemia?
Early-intense congestion
dusky/purple/blue
Lumen – sanguinous mucin
Arterial sharp demarcation
Venous fade gradually
What is the histology for acute ischaemia of the colon?
Oedema
Interstitial haemorrhages
Sloughing necrosis of mucosa-ghost outlines
Nuclei indistinct
Initial absence of inflammation
1-4 days –bacteria-gangrene and perforation
Vascular dilatation
What does chronic ischaemia of the colon cause?
Mucosal inflammation
Ulceration
Submucosal inflammation
Fibrosis
Stricture
What is radiation colitis?
Radiation colitis, an insidious, progressive disease of increasing frequency, develops 6 mo to 5 years after regional radiotherapy for malignancy, owing to the deleterious effects of the latter on the colon and the small intestine.
Abdominal irradiation can impair the normal proliferative activity of the small and large bowel epithelium
Usually rectum- pelvic radiotherapy
Damage depends on dose
Radiation to what organs can cause radiation colitis?
Targets actively dividing cells esp. blood vessels
and crypt epithelium
symptoms radiation colitis?
anorexia; abdominal cramps; diarrhoea and
malabsorption
What does the damage of radiation colitis depend on?
the dose
What does the presentation of chronic radiation colitis mimic?
IBD
What is the histology of radiation colitis?
Bizarre cellular changes
Inflammation-crypt abscesses and eosinophils
Later-arterial stenosis
Ulceration
Necrosis
Haemorrhage
perforation
What is inflammation of the appendix called?
Appendicitis
What is the average size of the appendix?
Average 6-7cm
What is the appendix?
The appendix is a small, finger-shaped organ that comes out of the first part of the large intestine.
What happens to the appendix with age?
Prominent lymphoid tissue regresses with age
Fibrous obliteration
What does appendicitis cause for the appendix?
Cause-obstruction e.g. feocolith or Enterobius vermicularis
Increased intraluminal pressure- ischaemia
What is appendicitis a form of?
Acute inflammation
How can appendicitis lead to ischaemia?
Increased intraluminal pressure-
What is the histology of appendicities?
Macro- fibrinopurulent exudate, perforation, abscess
Micro-
Acute suppurative inflammation in wall and pus in lumen
Acute gangrenous-full thickness necrosis +/- perforation
What is a large bowel neoplasia?
A benign or malignant neoplasm that affects the colon
What are polyps?
A polyp is a projecting growth of tissue from a surface in the body, usually a mucous membrane. Polyps can develop in the: colon and rectum. ear canal. cervix.
What is dysplasia?
Dysplasia refers to the abnormal development of cells within tissues or organs. It can lead to various conditions that involve enlarged tissue, such as hip dysplasia. It can also lead to the formation of precancerous cells. Dysplasia can occur in any area of the body and can vary in degree of severity.
What are the 2 stages of large bowel neoplasia?
Dysplasia
Low grade
High grade
Malignancy
Colorectal carcinoma
What can be seen in high grade large bowel neoplasia?
Carcinoma in situ
Crowded
Very irregular
Not yet invasive
What can be seen in low grade large bowel neoplasia?
Increased nuclear nos.
Increased nuclear size
Reduced mucin
What can large bowel neoplasia lead to?
Colorectal Adenocarcinoma
What is the most common histological type of colorectal carcinoma?
Colorectal Adenocarcinoma
What are risk factors for colorectal carcinoma?
Lifestyle
Family history
IBD [UC and Chrons disease]
What gene mutations are linked to colorectal carcinoma?
FAP
HNPCC
Peutz-Jeghers
What percentage of dysplasia in the colon are solitary?
50%
Q
What is the clinical presentation of left sided colorectal adenocarcinoma?
Annular
Napkin ring lesion
Bleeding
Fresh/altered blood PR
Altered bowel habit
Obstruction
Q
What are is the clinical presentation of right side colorectal adenocarcinoma?
Exophytic/Polypoid
Anaemia
Altered blood PR
Vague pain
Weakness
Obstruction
What does prognosis of colorectal carcinoma depend on?
Tumour grade
Tumour Stage
TNM
T1-4
N1-2
M0-1
Dukes’
A, B, C1/C2
Extramural venous invasion
Resection
What does Dukes classification consider?
The first variant of Dukes’ classification included three stages, based on the extent of tumor spread
What are the different grades for dukes classificaion?
Dukes A: Invasion into but not through the bowel wall.
Dukes B: Invasion through the bowel wall penetrating the muscle layer but not involving lymph nodes.
Dukes C: Involvement of lymph nodes.
Dukes D: Widespread metastases.