PathCAL

Question 1

Typical presentation of Crohn’s

Answer 1

• Diarrhoea
• Rectal bleeding
• Weight loss
• Anaemia= iron deficiency

Question 2

What does Crohn’s look like in endoscopy?

Answer 2

• Red areas= ulceration
• Raised areas protruding into lumen
• Yellow material on surface= fibrin (fibrinous exudate derived from acute inflammatory response)

Question 3

What do we see in biopsy in Crohn’s?

Answer 3

• Crypts show variation in shape and size
• Clear mucin still present, patchy
• Clear spaces in lamina propria, due to oedema: the fluid itself washes out when the tissue is dehydrated during processing, but spaces remains where it was.
• Lots of cells (dark-staining nuclei) in some parts of the lamina propria, although not in others.
• Neutrophil polymorphs in the lamina propria, indicating acute inflammation.
• Lymphocytes and plasma cells in the lamina propria, indicating chronic inflammation.
• More obvious mucin depletion in crypt epithelium: there’s relatively little mucin now.
• Markedly increased numbers of cells in lamina propria.
• Collections of cells with elongated nuclei and pink cytoplasm: these are epithelioid macrophages= granuloma

Question 4

Why is biopsy of the distal large intestine not diagnostic in crohn’s

Answer 4

• Small and includes mainly the mucosa and a little submucosa. Bigger there would be a risk of perforating the intestine.
• Similar to UC
• If we don’t have the deeper layers of the bowel wall, which are affected in Crohn’s disease, then we can’t see the more characteristic features that allow us to diagnose it.
• Patchy and affects different areas of the intestine. If we have biopsies only of certain small areas we can’t map out these changes along the bowel.
• Small intestine as well as the large intestine. If we have changes in the small intestine (apart from the terminal ileum, where there’s sometimes a so-called backwash ileitis in ulcerative colitis) then we can rule out ulcerative colitis but it’s more difficult to biopsy the small intestine.
• If we find granulomas, then it helps orientate the diagnosis towards Crohn’s disease, but we can find small granulomas in the superficial mucosa in ulcerative colitis, usually due to foreign body damage by faeces or something.

Question 5

What agents are useful in Crohn’s management?

Answer 5

• Prednisolone= corticosteroids, active stage so induce remission, budesonide
• Sulphasalazine= salicylates suppress inflammatory response, mesalazine
• Azathioprine= continually relapsing Crohn’s, thiopurine dug induces apoptosis of T lymphocytes
• Anti-TNF antibodies= infliximab and adalimumab induce apoptosis of T lymphocytes
• Nutritional therapy- polymeric or elemental diet

Question 6

Why might surgical intervention be required for Crohn’s?

Answer 6

• Intestinal obstruction: due to a stricture of the bowel.
• Fistula: to bladder, bowel, skin, vagina etc.
• Perianal disease: fissures, fistulae.
• Failure of medical treatment.

Question 7

How does cobblestoning occur?

Answer 7

Oedema of the submucosa.

Fissures, which extend into the submucosa and undermine the mucosa.

Question 8

What is pneumaturia?

Answer 8

• Fistula between intestine and bladder

- Patient would pass air during micturition

Question 9

What are the intestinal complications of Crohn’s?

Answer 9

• Malabsorption if in small intestine (terminal ileum= vitamin B12)
• Subacute intestinal obstruction due to strictures and adhesions
• Acute toxic dilation
• Perianal abscesses
• Fistulae

Question 10

What types of anaemia are associated with Crohn’s?

Answer 10

• Iron deficiency
• Megaloblastic= malabsorption of vitamin B12
• Folate deficiency

Question 11

What are the extra-intestinal complications of Crohn’s disease?

Answer 11

• Skin disorders= erythema nodosum, pyoderma gangrenosum
• Joint involvement= arthritis of large joints, sacroiliitis, ankylosing spondylitis
• Eye complications= conjunctivitis, uveitis
• Gallstones= reduced bile salt reabsorption from distal small intestine affecting enterohepatic circulation of bile

Question 12

What genetic factors are linked to Crohn’s?

Answer 12

NOD2

• Nucleotide oligomerism binding domain 2
• NOD2 encodes protein that binds to bacterial peptides inside cells, activates gene NF-kB
• Mutations of NOD2 create certain variants that are less effective in recognising and destroying bacteria in the lumen of the intestine

-ATG16L1
-IRGM
=Genes that recognise and respond to antigens inside cells

Question 13

The immunes response in IBD

Answer 13

In people with Crohn’s disease there tends to be a preponderance of helper T lymphocytes, of the TH1 type and maybe also the TH17 type.

In ulcerative colitis, by contrast, there seems to be a greater dominance of TH2 lymphocytes.

The importance of the immune response underpins various forms of therapy of inflammatory bowel disease with immunosuppressant agents

Question 14

What are the epithelial defects in Crohn’s?

Answer 14

• Defects in the tight junctions in the intestine of patients with Crohn’s disease and also in their relatives.
• There’s also a disorder of the transport of materials across the epithelial cells. A transporter called SLC22A4 is mutated.
• There are also polymorphisms of extracellular matrix protein 1 (ECMP1) in ulcerative colitis. ECMP1 inhibits matrix metalloproteinase 9.
• Also, in people with Crohn’s disease who have mutations of ATG16L1 there are defects in the Paneth cell granules. These contain antibacterial peptides called defensins.

Question 15

Typical presentation of ulcerative colitis

Answer 15

• Weight loss
• Diarrhoea, blood mucus and pus
• Tender left iliac fossa

Question 16

What does ulcerative colitis look like in biopsy?

Answer 16

• Irregularity of the surface: it’s not smooth and flat, as we saw in the normal colon.
• Crypts of different shapes and sizes (a): some are dilated and have angulated edges, while others are small. These changes are collectively termed crypt distortion.
• The clear mucin is no longer so evident: it’s been lost from many of the epithelial cells, the cytoplasm of which now stains bluish= mucin depletion
• lots of cells in the lamina propria= Collections of neutrophil polymorphs in the crypts, lots of cells in the lamina propria.= abscess so cryptitis

Question 17

What can be seen on a barium enema in UC?

Answer 17

• Straight bowel walls, due to loss of haustrations.

- Stippling, which is due to tiny ulcers. The barium goes into the ulcer craters and outlines them.

Question 18

What agents are used in ulcerative colitis management?

Answer 18

• Corticosteroids= prednisolone (induce remission, not long term)
• Azathioprine
• Mesalazine aminosalicylates reduce inflammatory reaction so maintain remission
• Methotrexate= anti inflammatory
• Ciclosporin= suppresses expansion of T cells

Question 19

Describe UC prognosis

Answer 19

• 10% get worse. If the symptoms get really bad, the patient may require surgical intervention, that is, removal of the diseased portion of colon, even if that’s the whole colon.
• 10% continue to have symptoms, but of fluctuating severity.
• 10% get better and don’t get any recurrence.
• most (70%) cases, we can expect a series of relapses and remissions. The patient gets better for a while, but then gets symptoms again for a while.

Various things can bring on relapses like this. Emotional stress, is one; treatment with antibiotics or NSAIDs is another; infections, such as gastroenteritis, are another.

This can continue for a long time: often for years.

Question 20

What is a proctocolectomy?

Answer 20

Operation to remove the entire colon and rectum

Question 21

What are the complications of UC?

Answer 21

• Hemorrhage
• Electrolyte disturbance
• Perforation of colon
• Dilation of colon
• Malignant change

Question 22

What is toxic megacolon?

Answer 22

Colon suddenly dilates

Question 23

What term is used to indicate the whole of the colon is inflammed?

Answer 23

Pancolitis

Question 24

What is steatorrhoea?

Answer 24

Passing pale, bulky faeces- fat

• IBS
• Coeliac
• Cystic Fibrosis

Question 25

What is shown in blood examination in coeliac disease?

Answer 25

``` The rim of haemoglobin is thinner. The clear zone in the centre is bigger Erythrocytes -Microcytic (smaller than usual) -Hypochromic (less haemoglobin than normal) ```

Question 26

Describe a biopsy in coeliac disease

Answer 26

- Villi: these are sticking upwards and are clearly seen. - Crypts of Lieberkühn: these are short, compared with the villi. - A few cells in the lamina propria, which underlies the epithelium. The nuclei of the cells are stained blue with the haematoxylin, although it's difficult to make out much more at this magnification - Villi are absent: we can't really make out any here. - The crypts are elongated, both in absolute terms and relative to the length of the villi. - There are increased numbers of dark-staining nuclei (i.e. cells!) in the lamina propria.

Question 27

What is subtotal villous atrophy?

Answer 27

The term subtotal villous atrophy has long been used, as the villi were thought to be visible as short, stubby remnants. -In addition to the short villi, the crypts undergo hyperplasia and therefore become longer than normal. This, too, reduces the villus: crypt ratio further.

Question 28

What are enterocytes?

Answer 28

columnar epithelial cells covering the intestinal mucosal surface

Question 29

What is the body's response in coeliac disease?

Answer 29

- Cell mediated response: genetically determined. - Humoral response: many patients have antibodies to gliadin in the blood, lymphocytes infiltrate - Crypt hyperplasia Shortening of villi. Lengthening of crypts. Increase in chronic inflammatory cells (lymphocytes, plasma cells) in the lamina propria and within the epithelium (increased intraepithelial lymphocytes). Damage to the epithelium: to the enterocytes

Question 30

What are long-term complications of coeliac disease?

Answer 30

- Carcinoma of small intestine | - Intestinal lymphoma