PBL 4 Flashcards
What are Haustrations?
Mixing movements that occur in the large intestine
Where the 3 longitudinal teniae coli contract at the same time
These call the unstimulated portion to bulge outwards into Haustrations
What is use of Haustrations?
Allow fecal matter to all be gradyllary exposed to the mucosal surface, allowing for absorption
What is a mass movement?
A modified type of peristalsis that occurs in the colon
Where are I cells found and what do they secrete?
Found in the small intestine, they secrete CCK
Name two incretin hormones?
Where are they secreted
GIP (gastrin inhibitory peptide) - dueodenum and jejunum
GLP-1 (glucagon like peptide 1) - small and large intestines
Where is motilin secreted?
In the duodenum and jejunum
How is motility in the gut controlled by the ENS by local reflexes?
Behind the bolus:
- Excitation of inner circular muscle - by Ach and substance P
- Inhibition of outer longitudinal muscle - by NO and VIP
In front of bolus
- Excitation of outer longitudinal muscle - by Ach and substance P
- Inhibition of inner circular muscle - by NO and VIP
What effect does noradrenaline have on the motility of the gut
Reduces motility
What is the effect of CCK on the sphincter of oddi?
CCK acts on local enteric nerves to cause release of inhibitory neurotransmitters NO and VIP to the sphincter of oddi
This causes the sphincter to relax, so bile and pancreatic juices can come through the ampulla of vater
How do enterochromaffin cells control GI tract motility?
Enterochromaffin cells are present in the GI tract and are stimulated by chemicals or mechanical touch
Enterochromaffin cells release 5-HT which plays a big role in contraction and relaxation of the gut wall
What neurotransmitter is released from enterochromaffin cells?
Serotonin
How do opiates lead to constipation?
Opiates act on Mu Receptors present in the GI Tract
This results in G protein activation which acts through second messengers to reduce nerve signals
Decreased excitatory nerve signals leads to a decrease in gut motility
Decreased gut motility leads to increased transit time so more water is absorbed, causing greater compaction of feces
How does Imodium relieve diarrhoea?
It is an opoid mu receptor agonist
Therefore acts to inhibit gut motility by decreasing the activity of the myenteric plexus
How do the external and internal anal sphincter differ in their control?
Internal sphincter - autonomically controlled
External sphincter - somatically controlled
What are the two reflexes in the defection reflexes mediated by?
Short reflex - ENS myenteric nervous system
Long reflex - vagus nerve
Why is the colour of feces brown?
Because of stercobilin and urobilin
What type of antibody is present on the simple coloumnar epithelium in the gut?
IgA
How can C.Diff infection be treated?
Fecal Transplant therapy
How does a healthy microbiome help in immunity
Gut bacteria stimulate the secretion of antimicrobial peptides from paneth cells
Where are stem cells found in the gut?
At the bottom of crypts in between paneth cells
What is gut associated lymphoid tissue?
Pop up lymph nodes within the gut which contain an abundance of immune cells
What is special about the dendritic and macrophage cells lining the gut epithelium
They are able to ‘sample’ bacteria, taking it into the lymph node to see if it is friendly or not
What is cell atrophy?
Cell shrinking?
What is the difference between cell hypertrophy and hyperplasia?
Hypertrophy - cell increase in size
Hyperplasia - increase in the number of cells due to cell division
What are the three types of cell growth in cancer?
Metaplasia
Dysplasia
Anaplasia
What are the different cyclin/cdk partners required for progression through the different stages of the cell cycle?
Cyclin B/CDK1: from G2 to mitosis
Cyclin D/CDK4: G1 stage beginnning
Cyclin E/CDK2: G1 stage end
Cyclin A/CDK2: S phase
In the wnt signalling pathway, what happens when wnt is not bound?
GSK-3B is able to phosphorylate beta-catenin
This causes beta-catenin to be targeted for proteolytic degradation
In the wnt signalling pathway, what happens when wnt is bound?
When wnt is bound, it disrupts the intracellular protein complex, so GSK-B is switched off
B-catenin is not phosphorlated and targeted for degradation
B-catenin moves into the nucleus - acts a transcription factor resulting in increased gene expression and cell proliferation
How do wnt and Ras regulate induce the S phase of the cell cycle?
Wnt and Ras both lead to an increase of transcription of cyclin D1
Cyclin D1 activates CDK4
CDK4 phosphorylates Rb
This releases E2F from Rb, and E2F then enters the nucleus to cause transcription of cyclin E
Cyclin E binds to CDK2 to trigger S phase of the cell cycle
How does p53 act as a tumour suppressor in the cell cycle?
P53 is a transcription factor which upregulates the transcription of p21
P21 inhibits CDs, inhibting the different phases of the cell cycle
What is the TMN staging in cancer?
T = size of tumour N = number of lymph nodes involved M = if it has metastasised or not
What is a colorectal polyp
An overgrowth of epithelial cells that overlies the colon or rectum
What is the pathophysiology of a polyp
At the bottom of colonic crypts you have stem cells which divide into daughter cells and migrate up and out
Overproliferation of these stem cells results in an early adenomatous polyp
What is APC
It is a tumour suppressor gene in the wnt signalling pathway
How can familial adenomatous polyposis (FAP) predispose an individual to developing colorectal cancer?
Mutation in APC allows beta-catenin signalling to occur even in the absence of wnt
This stimulates the migration of malignant stem cells out of the colon crypts
These produce 1000s of polyps along the colon wall
What are the two well defined familial forms of colorectal cancer?
Familial adenomatous polyposis (FAP)
Hereditary non-polyposis colorectal cancer (HNPCC)
What is the pathophysiology of hereditary non-polyposis colon cancer (HNCC)
Mutations found in mismatch repair genes
This means mutations are more likely to occur
This causes microsatellite instability
This can lead to mutations in TGF-beta
TGF beta is normally responsible for antiproliferative signals - when it is mutated this leads to proliferation
What are the genes that are used in mismatch repair?
MutSa (MSH6 & MSH2)
MutLa (MLH1 & PMS2)
What % of colorectal cancer is a mutation in MLH1 found?
15%
What % of colorectal cancer are mutations in TGF-beta found in?
90%
What is the normal function of TGF-Beta
Binds to its extracellular receptor, causing intracellular signalling cascade via Smad proteins, this results in:
- Activation of CKIs: inhibit cell proliferation
- Inhibition of MYC: inhibit cell proliferation
What are the 4 stages of colorectal cancer?
Stage 0 - not passed mucosa Stage 1 - beyond mucosa, no lymph nodes Stage 2 - entire gut wall, no lymph nodes Stage 3 - lymph nodes Stage 4 - distant organs (metastatic)
What is the most common site of metastasis for colorectal cancer?
Colon cancer - metastasises to liver
Rectal cancer - metastasises lungs
What are the clinical features of a right sided colon cancer?
Weight loss
Abdominal pain
Bleeding
Fatigue and weakness
What are the clinical features of a left sided colon cancer?
Infiltrating mass
Obstruction of bowel
How is colorectal cancer diagnosed?
Colonoscopy - take biopsy
Contrast barium enema - look for apple core sign
Fecal occult blood test - look for blood
What are the common chemotherapy drugs used to treat colon cancer?
Oxaliplatin
Fluorouracil (5-FU)
Folinic Acid (Leucovorin)
