GIS11 Pathology Of Small And Large Bowel Flashcards
Common diseases of small and large intestines
- Intestinal obstruction (anywhere in intestine —> digested food, faeces, mucus unable to pass through obstructed part —> intestine swells up —> ischaemic +/- perforate —> life-threatening)
- Mechanical
—> Physical blockage (e.g. tumour, external compression, solid objects)
—> Extramural / Mural / Luminal - Functional (pseudo-obstruction)
—> no mechanical blockage
—> Paralytic ileus (intestine stop peristalsis)
—> very ill patient (sepsis) / after abdominal surgery
- Ischaemic bowel disease
- Diverticular disease of colon
- Inflammatory bowel disease (Crohn’s disease + ulcerative colitis) (idiopathic)
- Neoplasms of intestine
- Intestinal polyps
- Colorectal carcinoma
Intestinal obstruction causes
- Extramural:
- *Adhesion (previous surgery create adhesion bands —> interfere with peristalsis)
- *Hernia (protrusion of abdominal organs into orifice e.g. inguinal / femoral canal)
- *Volvulus (intestine twist around itself —> obstruction and strangulation)
- External compression - Mural:
- *Tumour
- *Intussusception (一段腸道套入另一段腸道, intestinal wall gets caught in peristaltic wave and gets carried along —> 縮窄腸道)
- Strictures from previous inflammation - Luminal:
- Foreign object
- Parasite
- Bezoar - Functional obstruction
- *Paralytic ileus
*common
Intestinal obstruction signs and symptoms
- ***Absolute constipation
- no defecation / passage of flatus (gas) - ***Abdominal distension
- peristalsis may be visible on abdominal wall - ***Colicky pain
- caused by intense peristalsis
- pain comes and goes in waves - Vomiting
- more common in proximal small intestinal obstructions
Intestinal obstruction complications
Increasingly distended by fluids and gases
1. **fluids and electrolytes excreted into distended intestine
—> **shock, electrolyte imbalance
- increased luminal pressure compresses blood vessels in intestinal wall (esp in closed loop obstruction)
—> intestinal **ischaemia
—> **perforation
—> acute peritonitis
Intestinal obstruction diagnosis
Physical examination:
- ***Abdominal distension, visible peristalsis waves
- ***Hyperactive bowel sounds (except Paralytic ileus: Hypoactive)
- Visible hernia
X-ray:
- ***Dilated bowel loops on supine abdominal X-ray
- ***Multiple fluid levels on erect abdominal X-ray
- Sigmoid volvulus (visible)
- ***Contrast follow-through (delineate level of obstruction)
- CT scans (look for masses)
Ischaemic bowel disease - blood supply
—> ischaemic enteritis (small intestine)
—> ischaemic colitis (large intestine)
Ischaemic enteritis —> small intestine
Ischaemic colitis —> large intestine
- Superior mesenteric artery
- Jejunum (jejunal artery)
- Ileum (ileal artery)
- Cecum (ileocolic artery)
- Ascending colon (right colic artery)
- Transverse colon (middle colic artery) - Inferior mesenteric artery
- Descending colon (left colic artery)
- Sigmoid colon (sigmoid artery)
- Proximal rectum (superior rectal artery) - Left and right internal iliac arteries
- Distal rectum (middle and inferior rectal artery)
Causes of ischaemic bowel disease
- Acute occlusion of arterial supply
- blood supply to a segment of intestine cut off
- Thrombosis, embolism, ruptured atherosclerotic plaque, vasculitis etc.
- ***Dusky serosa of gangrenous part —> transition zone between viable part and gangrenous part - Chronic ischaemia
- Decreased blood supply over a long period of time (months)
- Usually due to Atherosclerosis
- Mucosa of chronically ischaemic part of intestine —> ***fibrotic - Generalised hypotension
- decreased blood supply to entire GI tract
- Shock, severe blood loss
- bowel at **“watershed areas” most susceptible to damage (e.g. **splenic flexure: watershed zone between SMA and IMA) - Bowel strangulation
- Severe external compression of intestinal wall (intestinal obstruction)
- Sigmoid volvulus, strangulated hernia
- blood unable to flow to strangulated part of intestine —> ischaemia + gangrene
Acute bowel ischaemia signs and symptoms
- ***Sudden onset of abdominal pain
- ***Bloody diarrhoea
- ***Shock
- Fever and signs of peritonitis if perforation
- ***Metabolic acidosis on arterial blood gas (electrolyte imbalance, HCO3↓)
Acute bowel ischaemia diagnosis
- CT scan with IV contrast
2. Laparoscopy / Laparotomy
Diverticular disease
Diverticulum: outpouching of intestinal wall
True diverticulum:
- contains ***all layers of intestinal wall (mucosa, submucosa, muscularis propria, serosa)
- usually ***congenital
False diverticulum:
- only contains mucosa, some submucosal tissue, serosa, ***NO muscularis propria
- ***acquired
False Diverticular disease Pathogenesis
Low fibre diet, chronic constipation, hard stool
—> **increased intraluminal pressure from peristalsis
—> mucosa pushed through **defects in the muscularis propria (where blood vessels and nerves travel through the muscularis propria)
—> formation of diverticula
Diverticular disease signs and symptoms
- Usually asymptomatic
- Most common around sigmoid colon, but can appear anywhere along colon (rarely in small intestine)
- ***Acute diverticulitis (diverticulum becomes inflamed)
- ***Diverticular abscess (forms around the inflamed diverticulum)
- ***Acute peritonitis (diverticular abscess ruptures into peritoneum)
Idiopathic inflammatory bowel disease
Chronic inflammatory disorder of small / large intestine of unknown etiology
Major features:
- **Inflammation + **Ulceration of bowel mucosa
- Relapsing clinical course over many years
2 entities:
- Crohn’s disease
- Ulcerative colitis
***Crohn’s disease vs Ulcerative colitis
Crohn’s disease:
- affect ***entire GI tract (mouth to anus)
- ***skip lesions: normal bowel between 2 or more segments of inflamed bowel
- inflammation involves ***full thickness of bowel wall (transmural)
Ulcerative colitis:
- ***large intestine only
- ***continuous involvement from rectum to proximal colon, no skip lesions
- inflammation involves ***mucosa and submucosa only
IBD proposed pathogenesis
- Abnormal gut ***microbiota?
- Defects in **tight junctions between epithelial cells (genetic causes?)
—> increased intestinal permeability
—> influx of bacterial components
—> Activated T helper cells
—> **hyperactive mucosal immune response
***IBD morphology
Crohn’s disease
- Skip lesions
- Elongated ***serpentine (snake-like) ulcers
- Deep fissures between islands of relatively normal mucosa (cobblestone)
- Strictures, Thickened **rigid bowel wall (*lead-pipe)
- Fat wrapping around serosa (creeping fat)
Ulcerative colitis
- Continuous lesions beginning from Rectum
- ***Broad shallow ulcers
- Inflammatory ***pseudo-polyps (islands of regenerating mucosa between ulcers)
- Normal bowel wall
- Normal serosal surface
IBD clinical features
Crohn’s disease: - abdominal pain - diarrhoea - weight loss - malaise, anorexia, fever - extra-intestinal manifestations —> uveitis (eye) —> arthritis (joint) —> ankylosing spondylitis (spine) —> sclerosing cholangitis (liver and bile duct)
Ulcerative colitis:
- ***Bloody diarrhoea with mucus
- ***Lower abdominal pain
- malaise, anorexia (less severe)
- extra-intestinal (similar to Crohn’s)
IBD complications
Crohn’s disease 1. Intestinal ***obstruction (strictures) 2. Intestinal ***perforation (fissure) 3. ***Fistula formation (fissures) —> between bowel loops —> between bowel and urinary bladder —> between bowel and vagina —> between bowel and abdominal skin —> anal fistula 4. Increased risk of colorectal carcinoma
Ulcerative colitis
- ***Toxic megacolon
- severely dilated colon filled with gas
- impending perforation
- high mortality - Increased risk of colorectal carcinoma
Colon polyps
- proliferation of colonic epithelium into a raised or mushroom-shaped structure
- associated with increased risk becoming carcinoma (neoplastic polyps)
- major types:
- Hyperplastic polyps
- Adenomas
- Inflammatory polyps
- Harmatomatous polyps (proliferation of both epithelial and stromal cells, can be hereditary)
- Adenomas
Hyperplastic polyps
- ***Benign proliferation of colonic epithelium
- very common after 50-60 years
- gross morphology: ***mushroom-shaped mucosal protrusion
- microscopic morphology: elongated gland with serrated (saw teeth-like) surface
Adenoma
- **Neoplastic proliferation of colonic epithelium —> **potential to become carcinoma
- gross morphology: ***Pedunculated (elongated stalk) polyp
- microscopic morphology: Tubular, Villous, Tubulo-villous (not much clinical significance)
- ***Epithelial dysplasia present
—> degree of epithelial dysplasia (low grade / high grade) correlate with risk of becoming carcinoma
—> low grade: elongated nuclei
—> high grade: complex architecture, multiple branching gland, fusion of glands
Colorectal carcinoma
- Carcinoma from epithelium of large intestine
- Most common in HK by incidence
- age of onset: usually 60-70
Risk factors:
- Diet / Lifestyle: ***smoking, low intake of fibre, obesity, red meat and refined carbohydrate
- GI diseases: Crohn’s disease, Ulcerative colitis
- Genetics: positive family history, hereditary colorectal carcinoma syndrome
***Colorectal carcinoma morphology
Gross appearance:
- ***Polypoid mass (with central ulceration)
- ***Everted edges
- Constricting annular mass around colonic circumference (sometimes)
Microscopic appearance:
- Cuboidal to columnar cells forming irregular gland-like structures
- High N/C ratio, enlarged nuclei, severe variation in nuclear diameter
- Invasion beyond muscularis mucosae
Colorectal carcinoma Grading and Staging
Grading:
- Well / Moderately / Poorly differentiated
- Tumour graded on how much it resembles normal colonic epithelial cells
- Grade determine how much ***gland formation the tumour has
Staging:
- T: Depth of tumour invasion (into submucosa, into / beyond muscularis propria, perforate visceral peritoneum, invasion into adjacent organs)
- N: Number of regional lymph nodes with metastatic carcinoma
- M: Distant metastasis
***Colorectal carcinoma Signs and symptoms
Right colon (caecum, ascending) 1. Anaemia 2. Malaise 3. Weight loss (Stool still fluid in right colon —> can pass through tumour constriction —> not much change in bowel habit)
Left colon (left transverse, descending, sigmoid)
- Altered bowel habit
- ***Haematochezia (passage of fresh blood with stool)
- ***Tenesmus (feeling of incomplete defecation; if tumour in rectum)
- ***Intestinal obstruction
Adenoma-Carcinoma sequence in FAP
- Normal colon:
- Inherited / acquired mutations of Tumour suppressor gene (1st hit) (APC) - Mucosa at risk:
- methylation abnormalities/ inactivation of normal alleles (2nd hit) (***APC) - Adenomas:
- protooncogene mutations (KRAS)
- homozygous loss of additional Tumour suppressor genes / overexpression of COX-2 (p53, LOH, SMAD2, SMAD4) - Carcinoma:
- additional mutations, gross chromosomal alteration (telomerase, many genes)
Familial colorectal cancer syndrome
Familial adenomatous polyposis (FAP)
- autosomal dominant
- hundreds of adenomatous polyps in colon (pan-colonic)
- > 90% chance of developing into colorectal cancer by 50 years old
- skin and bone tumours (variant of FAP)
- brain tumours (variant of FAP)
- **- APC gene (tumour suppressor gene)
- **- APC/WNT pathway —> chromosomal instability
- **- diagnosis: Endoscopy: at least 100 polyps in the colon
Hereditary non-polyposis colorectal cancer (HNPCC, Lynch syndrome)
- autosomal dominant
- colon cancer (esp. proximal colon, little to no polyps)
- gastric carcinoma
- endometrial / ovarian carcinoma
- ureter and renal pelvis carcinoma
- biliary tract carcinoma
**- MSH2, MLH1
**- mutation in DNA mismatch repair pathway —> microsatellite instability
***- diagnosis: Amsterdam criteria II
—> 3 people in a family got colorectal cancer / non-GI tumours
—> 2 successive generations affected
—> 1 person is 1st degree relative
—> 1 person diagnosed before 50 years old
—> + NOT FAP (must satisfied)
