Where is the most common metastasis site for colon cancer?
Liver
Lower 1/3 of rectum is different to the rest of the colon and rectum how?
Bypasses portal circulation (blood drainage)
What are the two sub-types of inflammatory bowel disease? (IBD)
(What is the cause of each)
Crohns and ulcerative colitis
Both are autoimmune- genetic/ environmental factors
Name a big environmental risk factor for crohns disease?
Smoking
IBD affects people most commonly at what age?
15-45
Ulcerative colitis affects which area’s of the GI tract?
Sigmoid colon and rectum
Crohns affects which part of the GI tract?
All of it
Although doesn’t often affect rectum
Mouth ulcers are a specific symptom of which type of IBD?
Crohns
Crohns and ulcerative colitis show what patterns in the location of their inflammation?
Crohns: ‘Skip lesions’
Ulcerative colitis: “Continuous”
What are the symptoms of IBD?
Recurrent diarrhoea (can be bloody- more likely UC) Weight loss/ extreme tiredness Abdominal pain (more common in crohns)
What is the difference in the depth of inflammation of UC/ crohns?
UC: Just submucosal
Crohns: Transmural (through whole bowel wall)- Can lead to peritonitis-shock-death
What is the treatment for ulcerative colitis?
Mesalazine (first line)- reduce inflam
Steroids for flare up
Infliximab/ Ciclosporin
Azathioprine (Immunosupressant)
What effect does IBD (especially UC) have on the hasutra?
Flattens them out (inflam)
‘Leadpipe appearance’
How would you diagnosis IBD?
Colonoscopy
Can do biopsy to exclude malignancy
How do you differentiate when taking a history between IBD and bowel cancer?
AGE (single biggest factor- either side of 50)
What are the types of symptoms in IBS?
Constipation- Give laxative
Diarrhea- Give immodium (loperimide) / buscapan
What are the paracolic gutters?
Between colon and posterolat abdominal wall, immediatly lateral to ascending and decending colons. They allow spread of material from one part of peritoneal cavity to another (cancer/ infection)
What is the transverse mesocolon?
A fold of peritoneum connecting transverse colon with post abdo wall.
Attached to pancreas and greater ommentum
What is the marginal artery?
An anastamoses between R/Mid/ L coeliac arteries
it’s continuous
What is McBurney’s point?
Base of the appendix, often site of pain in appendicitis
1/3 of distance on line from ASIS to umbilicus
What is appendicitis and how does it’s incidence change with age?
Inflammation of the appendix due to lumen obstruction
Incidence decreases with age as lumen size also decreases with age
What is the rectosigmoid junction?
Teniae coli dissapear and replaced by longitudinal smooth muscle of rectum
What is the pectinate (dentate) line in the rectum?
Line which divides lower 1/3 and upper 2/3 of the rectum. Above the line no pain is felt but the lower 1/3 can feel pain
Where are anal valves/ sinus’ located?
Valves are located in a circle around the pectinate line, with each valve having a sinus just superior to it
How does the rectum differ to the rest of the colon?
it has no sacculations (haustra) or omental appendices, it follows the curve of the sacrum and enters the rectal ampulla then into the anal canal
What is a portal system?
Where a capillary bed drains into another capillary bed without first going through the heart
(So liver receives both oxygenated and deoxygenated blood)
How and where does the hepatic portal vein form?
Formed by union of sup mesenteric vein and splenic vein
Forms post to pancreas
How does the HPV travel to the liver? What structures does it travel with?
Through the hepatoduodenal ligament
Along with hepatic artery proper and bile duct
What is the function of the HPV and how does it enter the liver?
Drains all abdo viscera into liver
Divides into R/L branches before entering liver parenchyma
What are the 4 portal/ systemic anastamoses? What 3 pathologies are 3 of them linked with?
Submucosa of oesophagus (oesophageal varicies)
Submucosa of anal canal (haemorrhoids/ piles)
Paraumbilical region (caput medusae)
Transperitoneal veins
How are pathologies caused in the sites of anastamoses of the systemic and portal systems?
Portal hypertension leads to engourgement of these veins and then bleeding
What are haustra?
Bulging pouches in the colon caused by taniae coli contraction
Where do each of the three major GI tract lymph drainage sites lead to?
Coeliac/ sup mesenteric/ inf mesenteric LN’s drain to:
Intestinal trunks > cisterna chyli > Thoracic duct > L subclavian
Where is the cisterna chyli found?
Dilation of lymph vessel
Post to AA @ L1/L2
ALL splanchnic nerves are what type?
Preganglionic
What are the two diiferent types of splanchnic nerves and where do they arise from?
Sympathetic: From thoracic/ lumbar/ sacral sympathetic trunks > prevertebral plexus ganglion
Parasympathetic: From pelvis (ant rami S2-S4) to an extension of prevertebral plexus (hypogastric/ pelvic plexi)
How does villi differ in the Li and SI?
LI has deep crypts but no villi
LI secretes lots of mucus but no digestive enzymes
Which epithelial cells are found in the SI but not the LI?
Enterocytes/ enteroendocrine cells/ paneth cells
Why can broad spectrum AB’s be dangerous in the colon?
Kills good bacteria resulting in less competition for bad bacteria- can possibly lead to clostridium difficile infection
What are the 3 layers of the mucosa in the GI tract?
Epithelium
Lamina propria (BV’s etc- loose connective tissue)
Muscularis mucosa- Double layer SM
What lies deep to the muscosa in the GI tract?
Submucosa (loose connective tissue with larger BV’s/ lymph/ nerve)
Can contain mucus secreting glands
What lies deep to the submuscosa in the GI tract?
Muscularis propria (aka externa) Has inner (circular) and outer (longitudinal) smooth muscle layers for peristalsis In colon longitudinal muscle become tenaie coli
What lies deep to the muscularis propria in the GI tract?
Adventia
This is the outermost layer and is connective tissue covered by peritoneum. Also has vessels/ nerves
What is the main function of the LI?
Re-absorption of water
although the majority of water absorbed in SI
What is the compostion of feces?
75% water
5% bacteria
20% indigestible material/ dead cells
Where are bile salts absorbed?
In the terminal ileum (some in the caecum)
(the sent back to liver to be put back into bile)-
What are the most common bacteria in the colon?
Mainly anaerobes:
Enterocossus faecalis/ bacterioides fragilis/ escherichia coli
What are the functions of bacteria in the colon?
Vitamin K synth (50% of total)
Biotin synthesis (water solube vit for glucose metabolism)
Vitamin B5 synth (water sol vit for steroid synthesis)
Converts bilirubin to urobilogens/ stercobilogens
Breaks down peptides (producing waste)
What is vitamin K needed for?
Production of 4 clotting factors (incl prothrombin)
remember it is lipid soluble so needs fat in the diet in order to be absorbed
What is vitB5 and what is it needed for?
Synthesised by colon bacteria
Used for neurotransmitter and steroid synthesis
How is bilrubin processed by the colon?
Converted to urobilogens and stercobilagens by colonic bacteria
Some U+S then goes into blood and out via kidneys.
Most is converted by O2 to urobilns and stercobilins
What gives poo it’s colour?
Urobilns and stercobilins
Break down of peptides by colonic bacteria produces what?
1) Ammonium ions (absorbed by colon, send to liver for conversion to non-toxic then out via kidneys)
2) Indole and skatole (give faeces it’s odour)
3) Hydrogen sulphide (H2S)- Gives rotten egg smell
What are mass movements?
3-4 times per day for 10-30mins
Push from transverse colon right to rectum, inducing need for defecation. Stimulated by distension of duodenum Chyme can travel 30-80% colon length
What is haustral churning?
Mixing of chyme in adjacent haustra
The majority of colorectal tumours are of what type?
Adenocarcinoma (from polyps)
What are the three most common cancers in the UK?
1) Breast
2) Lung
3) Colorectal
What are the two biggest cancer killers in the UK?
1) Lung
2) Colorectal
(20% colorectal have metastasis on presentation)
What is the distribution of colorectal cancer between the colon and the rectum?
70% colon
30% rectum
What is the most common site for colorectal cancer?
Over 70% are lower descending/ sigmoid/ rectum
What is the lifetime risk and 10yr survival rate for colorectal cancer?
1 in 20
10yr Survival is 57%
What is the most common age of presentation of colorectal cancer?
60-65
What are the risk factors for colorectal cancer?
FHx under age 60/ genetics (FAP)
IBD/ UC/ Crohns
Sedentary/ alcohol/ smoking/ low fibre intake
Diabetes/ nullparity
What is the common series of acquired mutations in colorectal cancer?
c-ki-ras mutation (becomes ademoa)
APC loss (in-siu carcinoma)
DCC loss
p53 loss (invasive carcinoma)
Where is the APC gene located?
5q21
Where is the p53 gene located?
17p13
What are the most common S+S of colorectal cancer?
Change in bowel habits >6wks Loose stools Rectal bleeding/ iron deficiency anaemia Weight loss Jaundice and hepatomegaly if mets
How is colorectal cancer diagnosed?
Colonoscopy/ DRE
Do FBC/LFT
Dukes and TNM to stage
What is the NICE recommended chemo treatment for colorectal cancer?
FOLFOX
Folinic acid: Is an adjuvant (enhancer) of 5-FU
5-Flurouracil (irreversibly inhibits thymidylate synthase)
Oxiliplatin
What are the surgical treatment options for colorectal cancer?
Subtotal colectomy (remove LI, preserve rectum) Local excision (remove local wall- early stage) R/L hemicolectomy
What is an adenoma?
Benign tissue of epithelial glandular origin
What are the three common polyp types seen in the colon?
1- Hyperplastic- from hyperplasia 2- Inflammatory
(1+2 are most common and unlikely to become malignant)
3- Adenoma (pre-malignant polps)
What are the three subtypes of adenoma in the colon?
Tubular (75%)- most common and not malig likely
Tubulovilous (15%)- Mix of 1 + 3
Vilous (10%)- Mostly in rectal area, high malignancy risk, most commonly sessile (flat) and non-pedunculated
What featured of polyps increase their likelihood of becoming malignant?
Large size
Villous
Sessile (flat)
What is FAP?
Familial adenomatous polyposis (~1% CRC)
Rare autosomal dominant APC mutation
100/1000’s polyps form by age 16, turn malig by age 35
What % of CRC’s have mutations in the APC gene?
80-90%
What is attenuated FAP?
Develops later in life (44yo) with less (
What is HNPCC (aka lynch syndrome)?
Hereditary non-polyposis colon cancer (3% of all CRC)
Few polyps but fast progession to malig
Often mutations in DNA repair genes (hMSH1/2)
Presents earlier than sporadic CRC
What is Wnt?
A signalling molecule that causes cell growth
It binds to a frizzled (FZD) receptor and through ‘dishevelled (DVL)’ protein stops degradation of ‘B-catenin)
What is B-catenin?
A signal molecule that when levels rise binds to TCT transcription factor which increases cell proliferation by upregulating MYC and CYCLIN D1 genes
How does APC normally affect cell growth?
APC gene is a tumour suppressor
Together with GSK3B and other molecules it forms a complex which degrades ‘B-catenin’ by tagging it for phosphorylation and this limits cell growth
How does a mutation resulting in loss of the APC gene affect cells?
It means the complex which degrades ‘B-Catenin’ doesn’t form, this increases ‘B-catenin’ levels and increases cell proliferation by up-regulating transcription of MYC and CYCLIN D1 proteins
What are the different dukes stages?
And 5yr survival rate
A: In submucosa and muscle wall only- 90%
B: Breached muscle layer and wall (but no LN’s)- 70%
C1: Spread to immediate (pericolic) LN’s -35%
C2: Spread to higher (mesenteric) LN’s
D: Distal visceral mets - 5%
Most CRC’s are diagnosed when they are at which stage?
B
Faecal occult blood screening is offered to all those aged…?
What does a +ve result mean?
60-75
(looks for hidden blood)
2% of +ve results are cancer, 30% are polyps
How is a faecal occult blood test performed?
Stool and H2O2 are placed on paper
Haem in blood breaks down H2O2 so therefore blood is present
What is a paracrine hormone?
Only has effect in immediate vicinity
What are the two types of gut movements?
Segmentation- Mixing (Circular muscle)
Peristalsis- Propulsion + mass effect (longitudinal muscle)
What is the histological compostition of smooth muscle fibres in the GI tract?
Unstriated, irregular actin/ myosin pattern, long and thin in bundles of ~5000 fibres
What are slow waves and what is their frequency in different parts of the GI tract?
Regular contractions of gut
Stomach- 3/min Duodenum= 20/min Ileum= 10/min
Colon = 7/min
What is the role of interstitial cells of cajal? (ICC)
Integrate SM activity and act as pacemaker cells
What is interdigestion?
Digestion between meals
What are long reflexes?
Extrinsic nerves where PNS acts with ENS (So there is both ENS and CNS involvement)
What is the difference in SNS/PNS action on the GI tract in terms of mechanism?
SNS- acts direct on SM
PNS- acts indirectly on myenteric/ submucosal plexi
What are short reflexes?
Enteric NS only!
Often local distension = increased local motility