GI tract diseases Flashcards
IBD
a group of inflammatory conditions of the colon and s.intestine.. long term conditions involving inflammation of the gut
principle types of IBD
- crohns disease
- ulcerative colitis
UC effects
the large intestine
Crohns effects
any part of the digestive system from the mouth to the ans
symptoms of IBD
pain, cramps or swelling in the tummy
- bloody diarrhoea
- weight loss
- extreme tiredness
causes of IBD
genetics and problems with the immune system
treating IBD
-aims to relieve symptoms and prevent them from returning: including diet, lifestyle, medicine and surgery
medicines given for IBD
- aminosalicylate
- immunosuppressants
- biologics (antibody based treatment given by injection)
4) antibiotics
the immune system and IBD
after exposure to abundant intestinal bacterial antigens, innate immune cells such as dendritic cell and macrophages are activated
- leading to the overproducing of chemises and proinflammmaotry cytokeind
pro-infllamtory cytokines
TNF, IL-12, IL-23, IL-1, IL-6
cytokines induce the expression of
adhesion meolce receptors in endothelia cels which together with chemokine initiate leukocytes to the site
down regulating over activated innate and adaptive immune repsonses
can successful ameliorate IBD
Genes involved with IBD
NOD2
IBD5
IL-23R
AIEC
NOD2
intracellular sensor for bacterial peptidoglycan. Polymorphisms can result in reduced activation of NF-kB in response to bacterial peptidoglycan
IBD6
play a role in maintaining the integrity of epithelia barrier
IL-23R
play a role in a citation inflammatory response
AIEC
adhesive and invasive E.coli
which bacterium is less common in patients with IBD
Faecalibacterium prausnitzii- ant-inflammatory role
Biomarkes for IBD
- C-reactive proteins
- Feal calprotectin
- Stool lactoferrin
Diabetes
a group of metabolic disorders which cause high blood sugar over a prolonged period of time due to either B cells of the pancreas not producing enough insulin or not responding to stimuli which would trigger insulin release
Type 1
B cells don’t produce enough insulin
Type 2
Insulin resistance- where ell do not respond to insulin properly- a lack of insulin may also occur
symptoms of diabetes
frequent urination, increased thirst, increased hunger, tiredess
chronic hyperglycemia
signif risk to cardiovascular disease, neuropathy and microvascular damage
glycosuria
when glucose is found in the urine- usually filtered and reabsorbed
- if blood glucose reached the renal -threshold, then reabsorption mechanism of kidney becomes saturated and glucose will be found in urine
how is Type 1 treated
Since b cells are destroyed, insulin is not naturally produced, therefore control of blood glucose is achieved by injecting insulin
Usually starts in childhood
how is Type 2 treated
normal physiological response to insulin is impaired, meaning that blood glucose remains elevated for longer than normal after an oral doe of glucose or a meal
Insulin is also less effective at suppressing glucose output by the liver
Defect isnt to do with the receptor, but in the complex insulin signalling pathway
Treated through diet and exercise
risk factor of type 1
Genetic predisposition linked to human leukocyte antigen (HLA)
risk factor of type 2
Age Obesity Ethnicity Family history Western diet Physical inactivity City dwelling
Bowel cancer
cancer of the large intestine e.g. colon or rectal cancer. Relating to the tumour suppressor gene DCC being switched off –> polyp formation
DCC
acts as a tumour suppressor and photo-oncogene
what are DCCs
receptors found the CSM of colorectal epithelium
what are part of the intracellular part of DCC
kinases- these activate the MAPkinase cascade
ligand of DCC is
Netrin-1- binds to the receptor and stimulates MAPK cascade
if DCC is over expressed
more MAPK cascade- more cell proliferation
intracellular cascade after entrain binds to DCC
1)SRC kinases are attracted to intracellular portion of DCC receptor- phosphorylates it
2) promoting Grb2 to bind to the receptor
) then MAPK cascade commences
- cell migration and proliferation
DCC and Netrin
DCC’s are dependence receptors
What are dependence receptors (2)
- can act with netrin-1 bound: cause cell proliferation
2. without entrain-1: activates caspases- apoptosis
without Netrin
DCC’s are tumour suppressors- stoping overgrowth of tissue
Netrin is only expressed
at the bottom of villi
DCCs are expressed
all along- no ligand at the top of villus- stop overgrowth and polo formation- therefore proliferation at the bottom, cell death at the top
cell proliferation
at the bottom
cell death
at the top- causes apoptosis when entry doesn’t bind to DCC
if DCC is deleted via mutation
this process won’t happen- no apoptosis at the top of the villi- polyp formation due to over proliferation.
when DCC is deleted
proto-oncogene
when DCC is there
tumour suppressor
