5 - GI tract dysfunction Flashcards
what promotes cell cycle progression
cyclins
cdks
what stops cell cycle progressionq
cdk inhibitors
quiescence in the cell cycle
cells can exit and re-enter cell cycle through G0 phase
early phase of G0
mitogen-dependent
growth factors are required for progression beyond this point
once the cell progresses past the R point …
.. mitogens are no longer required for cell cycle progression
cancer stages
refers to the extent of the cancer
e.g. size of tumour, how far it has spread
TNM staging system
TNM staging system
T - size and extent of the main/primary tumour
N - number of nearby lymph nodes that have cancer.
M - whether the cancer has meta-stasized. This means that the cancer has spread from the primary tumor to other parts of the body.
name 4 types of eicosanoid
thromboxane
prostacyclin
prostaglandin
leukotriene
what two enzymes cut arachindonate
cycooxygenase (COX)
lipooxygenase
what do COX enzymes cut arachindonate into
prostacyclins H2
what are prostacyclin H2s cut into and what are they important for
prostaglandins - mucus in GI tract/pain/inflammation
thromboxane - clotting
prostacyclins - platelets
what cuts membrane phospholipids into arachindonic acid
phospholipase A2
inihbition of COX enzymes
NSAIDs
no prostaglandins produced
reduced pain/inflammation
potential stomach ulcers and gastric bleeding
what happens in G2
cell growth
proteins duplicated
what happens in G1
cell mass doubles
organelles copied
order of cell cycle
G1
S
G2
M
what happens in S phase
synthesis of complete copy of DNA
centrosome duplicates
order of stages in mitosis
prophase prometaphase metaphase anaphase telophase cytokinesis
where are the 3 cell cycle check points
late G1 (G1/S)
G2/M
metaphase-anaphase
function late G1 checkpoint
checks integrity of DNA
cell commits to cell cycle entry and chromosome duplication (occurs in S)
function of G2/M phase
checks proper chromosome duplication
checks environment is favourable
checks all DNA are replicated
triggers early mitotic events
cell cycle checkpoint metaphase-anaphase
checks proper attachment of kinetochore
stimulates sister chromatid separation
checks all chromosome are properly attached to the spindle
what is APC
adenomatous polyposis coli
tumour suppressor gene
negative regulator of B-catenin
somatic APC mutation
loss of binding to B-catenin
loss of inhibition of Wnt signalling
initiates tumour growth - loss of control of cell cycle
germline APC mutation
causes familial adenomatous polyposis
what is p53
tumour suppressor gene
involved in regulation of cell cycle and apoptosis
what triggers p53 production
DNA damagr
stress signal
defective p53
abnormal cell proliferation
cancer
function of mdm2
negative regulator of p53
maintains low conc of p53 at homeostasis
represses p53 by constant phosphorylation and ubiquitination
what is mdm2
negative regulator of p53
regulation of G1/S checkpoint
p53 activation stimulates p21
cell cycle arrest
function of p21
stimluated by p53
cdk inhibitor p21-CDK2 complex causes cell cycle arrest
what is ras
family of small gtp-ases
membrane-associated guanine nucleotide binding protein
function of ras
regulates genes involved in cell growth, differentiation, survival
acts as an ‘on’ or ‘off’ switch
GDP bound
resting state
ras as a proto-oncogenes
mutant ras is always ‘on’
leading to continuous growth and proliferation
examples of mitogens that bind to RTKs
vegf - insulin
growth factor
outline steps in MAPK cascade
ligand binds receptor dimerisation + transautophosphorylation Grb2 binds - SH2 domain SOS (GEF) activates Ras by GTP exchange Ras.GTP complex phosphorylates Raf raf phosphorylates MEK MEK phosphorlates ERK ERK translocates to nucleus phosphorylation of transcription regulators transcripton
mitogen
protein that binds and induces cell division and therefore mitosis
when does the MAPK cascade stop
when a GTPase hydrolyses Ras.GTP to Ras.GDP
importance of DNA repair genes
detect damaged DNA
repair DNA to facilitate accurate DNA replication
mechanism of DNA repair genes
detect damaged dna e.g. hypoxia/cell injury
phosphorylate and activate p53
p53 transcribes apoptotic factors
p53 activates p21 - cell cycle arrest via CDK2
example of DNA repair gene that is also a tumour suppressor
BRCA1
BRCA2
longest wavelength on electromagentic spectrum
radio waves
effect of longer wavelength on frequency and energy
longer wavelength = lower frequency and lower energy
relationship between energy and wavelength
energy is directly proportional to wavelength
radiotherapy as cancer treatment
x-rays targeted at tumours
ionising radiation causes cell death
cell cycle arrest
induced apoptosis
whaat measurements are taken to TNM stage a patient
x-ray
lab test
N in TNM staging
number of nearby lymph nodes that are cancerous
uses of TNM staging
help plan treatment - indication of prognosis
assist in evaluation of results
indentify relevant clinical trials
enable global collation of information
3 stages of gastric acid secretion
cephalic phase
gastric phase
intestinal phase
what initiates cephalic phase
smell or taste of food
hunger
what mediates cephalic phase
parasympathetic and enteric (submucosal plexus) NS
when does cephalic phase of gastric secretion take place
before food has entered stomach
when does gastric phase of secretions take place
when food arrives in stomach
what effects does the presence of gastrin have
HCl secreted from parietal cells
histamine produced
histamine production…
increases HCl produtcion
why is HCl needed for digestion
to create acidic environment
proteins increase the pH
why is intestinal phase of gastric secretions important
promotes continued digestion in small intestine
what inhibits intestinal phase gastric secretions
CCK
somatostatin
secretin
which nutrients are absorbed in intestine
proteins
carbohydrates
lipids
protein absorption in intestine
brush border enzymes break peptides into amino acids in GI tract
amino acids transported by active transport from GI tract into enterocytes
peptides co-transported by PepT1 into enterocytes, then broken down into amino acids by peptidases
how are absorbed proteins transported from enterocytes to liver
via hepatic portal vein
carbohydrate absorption in intestine
enzymes break carbohydrates into monosaccharides facilitated diffusion (Na+/H+ exchange pump) GLUT channel-facilitated diffusion
lipid absorption steps
bile salts- emulsifies fat globules to fat droplets
lipase forms micelles (fat droplets surrounded by bile salts) which can directly pass through intestinal endothelium - across enterocytes
micelles form chylomicrons (tiny fat droplets)
how do absorbed fat droplets (chylomicrons) reach the liver
chylomicrons carried away by lacteals (lymphatic vessel) into lymphatic system into liver
2 diseases making up IBD
chrons
ulcerative colitis
