pathology transition Flashcards
what does vindicate stand for
vascular infection/inflammatory neoplastic drugs/toxins intervention/iatrogenic congenital/developmental autoimmune trauma endocrine/metabolic
cellular changes in response to increased demand
hyperplasia
hypertrophy
cellular changes in response to decreased demand
atrophy
cellular changes in response to altered stimulus
metaplasia
what are the two mechanisms for causing cell growth
increased production of growth factors
increased expression of growth factor receptors
what are the three classes of growth factor receptors
receptors with intrinsic tyrosine kinases
7 transmembrane G-protein-coupled receptors
receptors without intrinsic tyrosine kinases
what are the four main stages of the cell cycle
G1, S, G2, M
how is the cell cycle controlled
cyclin dependent kinases (CDKs)
what happens in phase G1 of cell cycle
cell gets bigger with increased protein synthesis
which CDK and cyclin are associated with G1
during G1, CDK4 is activated by cyclin D
what does CDK4 do in G1
phosphorylates the retinoblastoma protein
retinoblastoma protein is normally bound to
E2F
what is the function of E2F
kicks of cell division
how does retinoblastoma protein affect the action of E2F
stops it activating cell division
how does CDK4 activate cell division
CDK4 phosphorylates retinoblastoma protein so it can’t bind to E2F
when E2F is free, it is able to activate cell division
what happens in the S phase of cell division
synthesis phase
what molecular changes occur in the S phase
E2F initiates DNA replication
E2F increases levels of Cyclin A
Cyclin A activates CDK2 which also promotes DNA replication
what happens in G2 phase of cell cycle
cell gets bigger and more protein synthesis
what is main the checkpoint at the end of G2
p53
what is the function of p53
checks the cell for mistakes
if there are any the cell will apoptose
how is p53 important in the development of cancer
if p53 can be avoided by mutant cells they can keep dividing despite containing faults in their DNA
how are the number of cell divisions limited
chromosomes are capped with TTAGGG repeats
with every division the number of repeats gets smaller
examples of physiological hyperplasia
breast tissue during puberty
endometrium during pregnancy
examples of pathological hyperplasia
excess oestrogen leading to endometrial hyperplasia and abnormal bleeding
prostatic hyperplasia
lymph nodes in infection
is hyperplasia reversible or irreversible
reversible
how can hyperplasia be reversed
withdrawal of stimulus
eg hormones, infection
hyperplastic tissue is an at risk site for…
development of cancer
what is the difference between hyperplasia and hypertrophy
hyperplasia = more cells hypertrophy = bigger cells
when does cardiac hypertrophy become pathological
when the muscle requires more blood supply than it has so can no longer function properly
what is atrophy
reduction in cell size
examples of physiological atrophy
embryological structures
uterus after birth
examples of pathological atrophy
muscle atrophy due to decreased workload loss of innervation blocked blood supply loss of hormonal stimulation pressure ageing
which hormones promote degradation and atrophy
glucocorticoids
thyroid hormone
which hormones oppose atrophy and promote growth
insulin
what can cause acute inflammation
infection trauma foreign bodies immune reaction necrosis
what is the response to injury
vascular changes
cellular changes
chemical mediators
morphological patterns
what are vascular changes in response to injury
vasodilation of arterioles then capillary beds
mediated by histamine and NO
what does vasodilation result in
increased heat (calories) redness/erythema (rubor)
what are cellular changes in response to injury
stasis white cell margination rolling adhesions migration
how does injury affects the flow of cells within a vessel
blood normally flows centrally
vascular dilation slows the rate of flow and allows cells to more peripherally
what is white cell margination
movement of white cells from the centre of blood vessels to the periphery
what changes occur in the lumens surface of blood vessels in response to injury
express various proteins that allow white cells to bind to them
what are selectins are integrins
proteins expressed on endothelial cells and white cells respectively that bind together
what are VCAM and ICAM
vascular cell adhesion molecule
intercellular adhesion molecule
describe the integrin/selectin interaction
low affinity and binding on and off is fast
how do histamine and thrombin affect selectin expression
increased expression
what effect do TNF and IL1 have on expression of the endothelial proteins
increase expression of VCAM and ICAM
what is the effect of chemokine of the endothelial cell surface
bind to proteoglycans on endothelial cell surface to increase the affinity of VCAMs and ICAMs for integrins
how does injury cause swelling
leaky vessels leads to loss of protein
change in oncotic pressure means water follows protein into extracellular space
what makes blood vessels leaky
endothelial contraction: histamine, bradykinin, substance P, leukotrienes direct injury white cells transcytosis new vessel formation
what is chemotaxis
movement of cells along a chemical gradient
what are the three stages of phagocytosis
recognition and attachment
engulfment
killing and degradation
what are clinical features of inflammation
rubor calor tumor dolor loss of function
what causes rubor
increased perfusion
slow flow
increased permeability of vessels
what causes calor
increased perfusion
slow flow
increased vascular permeability
what causes donor
mediated by prostaglandins and bradykinin
which inflammatory cell characterises acute inflammation
neutrophil
what are features of neutrophils
polymorphic nucleus
granules
define resolution
complete restoration of the tissue to normal after removal of inflammatory components
what is needed for resolution
tissue needs good capacity for repair
good vascular supply for delivery of white cells and removal or injurious agents
what is in pus
living, dying and dead cells
neutrophils, bacteria, inflammatory debris
in what type of damage is organisation and repair preferred to resolution
damage beyond the basement membrane
which cells are characteristic of chronic inflammation
lymphocytes
caseous necrosis is associated with
TB
what are the effects of no ATP on membrane transport
Na/K ATPase fails = increased K (swelling)
calcium pump fails (increased Ca)
what is the effect of increased intracellular calcium
stimulates;
- ATPase (further reduces ATP levels)
- phospholipidase (membrane damage)
- proteases (membrane and cytoskeleton damage)
- endonuclease (DNA damage and breakdown)
- mitochondrial permeability (release pro death factors)
what are the first signs of cellular hypoxic injury
cells shrink
become red
nucleus shrinks and becomes dark
marginal contraction bands appear
what occurs during the first 24 hours after hypoxic injury
cell contents leaked
complement cascade initiated
acute inflammation
neutrophils are replaced by
macrophages
macrophages are replaced by
fibroblasts
what do fibroblasts do following MI
gradually lay down collagen
occurs after 2 weeks and completes at 6 weeks
what are the two types of cell death
necrosis and apoptosis
is necrosis pathological or physiological
always pathological
what is a feature of coagulative necrosis
preservation of cell outline
what is liquefactive necrosis associated with
localised bacterial and fungal infections
necrosis within the brain
what is caseous necrosis
granulomatous inflammation with central necrosis
investigations for TB
culture, PCR and ZN stain
defined apoptosis
programmed cell death in response to specific signals
example of physiological apoptosis
removal of self-reactive lymphocytes
hormonal dependent invocation (uterine lining)
examples of pathological apoptosis
response to injury radiation chemotherapy viral infection cancers graft vs host disease
which factors are associated with the extrinsic pathway of apoptosis
TNF
Fas
Fas mutations often result in…
autoimmune diseases
what is the intrinsic pathway of apoptosis
mitochondrial pathway
how is the intrinsic pathway of apoptosis activated
growth signals promote anti-apoptotic molecules in mitochondrial membrane
when growth signals are removed they are replaced with Bax/Bak which increase permeability of releases proteins that stimulate caspases (proteases)
reduced apoptosis can result in
cancer
autoimmune disease
increased apoptosis can cause
neurodegernative disorders
morphology of apoptosis
cells shrink
chromatin condensation
cytoplasmic blebs (Cytoplasm breaks up)
macrophages come to revoke debris
define neoplasia
new growth not in response to stimulus
what is the only body part that has never been reported to undergo neoplastic change
lens of the eye
what is metaplasia
reversible change from one mature cell type of another mature cell type
what type of metaplasia is often found in response to injury or exposure to noxious stimuli
squamous metaplasia
example of metaplasia in the lung
pseudo stratified ciliated epithelium is exposed thermal/chemical injury (smoking) resulting in squamous metaplasia
example of metaplasia in the bladder
transitional epithelium is exposed to inflammation (catheter) resulting in squamous metaplasia
metaplastic tissue is at risk of
development of cancer
what is autonomous hyperplasia
no longer needs stimulus to occur
what is dysplasia
abnormal growth not in response to a stimulus
define invasion
growth beyond the basement membrane
what is carcinoma in situ
dysplasia affecting the whole of the epithelium but does not go beyond the basement membrane
what is. the commonest cancer in men
prostate
what is the commonest cancer in women
breast
what are the hallmarks of cancer
increase growth signals remove growth suppression avoid apoptosis achieve immortality become invasive make your own blood supply loss of DNA checks avoid the immune system
which mutation is diagnostic in burkitt lymphoma
t(8:14)
how does Bcl-2 prevent apoptosis
binds to bax/bak to stop mitchondria become permeable (doesn’t release capsases)
what is VEGF
vascular endothelial growth factor
an encapsulated lesion implies that it is slow/fast growing
slow
carcinomas arise from
epithelium
adenoma/adenocarcinoma arise from
glandular tissue
squamous epithelium can produce what types of tumour
papilloma
SCC
tumours of connective tissues are called
sarcomas
benign tumour of fat
lipoma
benign tumour of bone
osteoma
malignant cancer of bone
osteosarcoma
benign cartilage tumour
enchondroma
malignant cartilage tumour
chondrosarcoma
define ephelis, naevus, and melanoma
freckle
mole
malignant melanocytic tumour
stage vs grade
stage - how much its grown
grade - how differentiated it is
which cancers often present early
vocal cords (voice change) skin cancers (if you can see them) breast cancer (self-examine) testicular cancer (self-examine)
weight loss in cancer is known as
cachexia
risk factors for atheroma
smoking HTN hyperlipidaemia DM age sex (males) genetics
where does atheroma occur
sites of turbulent blood flow
normally branching sites
HDL and LDL: good or bad
HDL good
LDL bad
how does atheroma occur
primary endothelial injury
accumulation of lipids and macrophages
digestion of smooth muscle cells over ‘foamy’ macrophages
increase in size
deposition of smooth muscle changes lesion from fatty streak to
fibrofatty plaque
when is atheromatous narrowing of an artery likely to produce critical disease
it is the only artery supplying an organ or tissue
the artery diameter is small (coronary artery vs common iliac artery)
overall blood flow is reduced
what are complications of atheroma
stenosis
aneurysm
dissection
thrombosis and embolism
what is arterial stenosis
narrowing of the arterial lumen
reduced elasticity and flow
arterial stenosis can cause
tissue ischaemia
clinical effects of cardiac ischaemia
reduced exercise tolerance angina unstable angina MI cardiac failure
what is cardiac fibrosis
loss of cardiac myocytes and replacement by fibrous tissue
what are the consequences of cardiac fibrosis
loss of contractility
reduced elasticity and filling
arterial stenosis affecting the carotid arteries may cause
TIA
stroke
vascular dementia
arterial stenosis affecting the renal arteries might cause
hypertension and renal failure
arterial stenosis affecting the peripheral arteries may cause
claudication
foot/leg ischaemia
define aneurysm
abnormal and persistent dilatation of an artery due to a weakness in its wall
where is the commonest site of aneurysm formation
abdominal aorta
what are complications or aneurysm
rupture thrombosis embolism pressure erosion of adjacent structures infection
what is an arterial dissection
splitting within the media by flowing blood resulting in false lumen filled with blood within the media
