pathology transition Flashcards
1
Q
what does vindicate stand for
A
vascular infection/inflammatory neoplastic drugs/toxins intervention/iatrogenic congenital/developmental autoimmune trauma endocrine/metabolic
2
Q
cellular changes in response to increased demand
A
hyperplasia
hypertrophy
3
Q
cellular changes in response to decreased demand
A
atrophy
4
Q
cellular changes in response to altered stimulus
A
metaplasia
5
Q
what are the two mechanisms for causing cell growth
A
increased production of growth factors
increased expression of growth factor receptors
6
Q
what are the three classes of growth factor receptors
A
receptors with intrinsic tyrosine kinases
7 transmembrane G-protein-coupled receptors
receptors without intrinsic tyrosine kinases
7
Q
what are the four main stages of the cell cycle
A
G1, S, G2, M
8
Q
how is the cell cycle controlled
A
cyclin dependent kinases (CDKs)
9
Q
what happens in phase G1 of cell cycle
A
cell gets bigger with increased protein synthesis
10
Q
which CDK and cyclin are associated with G1
A
during G1, CDK4 is activated by cyclin D
11
Q
what does CDK4 do in G1
A
phosphorylates the retinoblastoma protein
12
Q
retinoblastoma protein is normally bound to
A
E2F
13
Q
what is the function of E2F
A
kicks of cell division
14
Q
how does retinoblastoma protein affect the action of E2F
A
stops it activating cell division
15
Q
how does CDK4 activate cell division
A
CDK4 phosphorylates retinoblastoma protein so it can’t bind to E2F
when E2F is free, it is able to activate cell division
16
Q
what happens in the S phase of cell division
A
synthesis phase
17
Q
what molecular changes occur in the S phase
A
E2F initiates DNA replication
E2F increases levels of Cyclin A
Cyclin A activates CDK2 which also promotes DNA replication
18
Q
what happens in G2 phase of cell cycle
A
cell gets bigger and more protein synthesis
19
Q
what is main the checkpoint at the end of G2
A
p53
20
Q
what is the function of p53
A
checks the cell for mistakes
if there are any the cell will apoptose
21
Q
how is p53 important in the development of cancer
A
if p53 can be avoided by mutant cells they can keep dividing despite containing faults in their DNA
22
Q
how are the number of cell divisions limited
A
chromosomes are capped with TTAGGG repeats
with every division the number of repeats gets smaller
23
Q
examples of physiological hyperplasia
A
breast tissue during puberty
endometrium during pregnancy
24
Q
examples of pathological hyperplasia
A
excess oestrogen leading to endometrial hyperplasia and abnormal bleeding
prostatic hyperplasia
lymph nodes in infection
25
is hyperplasia reversible or irreversible
reversible
26
how can hyperplasia be reversed
withdrawal of stimulus
| eg hormones, infection
27
hyperplastic tissue is an at risk site for...
development of cancer
28
what is the difference between hyperplasia and hypertrophy
```
hyperplasia = more cells
hypertrophy = bigger cells
```
29
when does cardiac hypertrophy become pathological
when the muscle requires more blood supply than it has so can no longer function properly
30
what is atrophy
reduction in cell size
31
examples of physiological atrophy
embryological structures
| uterus after birth
32
examples of pathological atrophy
```
muscle atrophy due to decreased workload
loss of innervation
blocked blood supply
loss of hormonal stimulation
pressure
ageing
```
33
which hormones promote degradation and atrophy
glucocorticoids
| thyroid hormone
34
which hormones oppose atrophy and promote growth
insulin
35
what can cause acute inflammation
```
infection
trauma
foreign bodies
immune reaction
necrosis
```
36
what is the response to injury
vascular changes
cellular changes
chemical mediators
morphological patterns
37
what are vascular changes in response to injury
vasodilation of arterioles then capillary beds
| mediated by histamine and NO
38
what does vasodilation result in
```
increased heat (calories)
redness/erythema (rubor)
```
39
what are cellular changes in response to injury
```
stasis
white cell margination
rolling
adhesions
migration
```
40
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
41
what is white cell margination
movement of white cells from the centre of blood vessels to the periphery
42
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
43
what are selectins are integrins
proteins expressed on endothelial cells and white cells respectively that bind together
44
what are VCAM and ICAM
vascular cell adhesion molecule
| intercellular adhesion molecule
45
describe the integrin/selectin interaction
low affinity and binding on and off is fast
46
how do histamine and thrombin affect selectin expression
increased expression
47
what effect do TNF and IL1 have on expression of the endothelial proteins
increase expression of VCAM and ICAM
48
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
49
how does injury cause swelling
leaky vessels leads to loss of protein
| change in oncotic pressure means water follows protein into extracellular space
50
what makes blood vessels leaky
```
endothelial contraction: histamine, bradykinin, substance P, leukotrienes
direct injury
white cells
transcytosis
new vessel formation
```
51
what is chemotaxis
movement of cells along a chemical gradient
52
what are the three stages of phagocytosis
recognition and attachment
engulfment
killing and degradation
53
what are clinical features of inflammation
```
rubor
calor
tumor
dolor
loss of function
```
54
what causes rubor
increased perfusion
slow flow
increased permeability of vessels
55
what causes calor
increased perfusion
slow flow
increased vascular permeability
56
what causes donor
mediated by prostaglandins and bradykinin
57
which inflammatory cell characterises acute inflammation
neutrophil
58
what are features of neutrophils
polymorphic nucleus
| granules
59
define resolution
complete restoration of the tissue to normal after removal of inflammatory components
60
what is needed for resolution
tissue needs good capacity for repair
| good vascular supply for delivery of white cells and removal or injurious agents
61
what is in pus
living, dying and dead cells
| neutrophils, bacteria, inflammatory debris
62
in what type of damage is organisation and repair preferred to resolution
damage beyond the basement membrane
63
which cells are characteristic of chronic inflammation
lymphocytes
64
caseous necrosis is associated with
TB
65
what are the effects of no ATP on membrane transport
Na/K ATPase fails = increased K (swelling)
| calcium pump fails (increased Ca)
66
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)
67
what are the first signs of cellular hypoxic injury
cells shrink
become red
nucleus shrinks and becomes dark
marginal contraction bands appear
68
what occurs during the first 24 hours after hypoxic injury
cell contents leaked
complement cascade initiated
acute inflammation
69
neutrophils are replaced by
macrophages
70
macrophages are replaced by
fibroblasts
71
what do fibroblasts do following MI
gradually lay down collagen
| occurs after 2 weeks and completes at 6 weeks
72
what are the two types of cell death
necrosis and apoptosis
73
is necrosis pathological or physiological
always pathological
74
what is a feature of coagulative necrosis
preservation of cell outline
75
what is liquefactive necrosis associated with
localised bacterial and fungal infections
| necrosis within the brain
76
what is caseous necrosis
granulomatous inflammation with central necrosis
77
investigations for TB
culture, PCR and ZN stain
78
defined apoptosis
programmed cell death in response to specific signals
79
example of physiological apoptosis
removal of self-reactive lymphocytes
| hormonal dependent invocation (uterine lining)
80
examples of pathological apoptosis
```
response to injury
radiation
chemotherapy
viral infection
cancers
graft vs host disease
```
81
which factors are associated with the extrinsic pathway of apoptosis
TNF
| Fas
82
Fas mutations often result in...
autoimmune diseases
83
what is the intrinsic pathway of apoptosis
mitochondrial pathway
84
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)
85
reduced apoptosis can result in
cancer
| autoimmune disease
86
increased apoptosis can cause
neurodegernative disorders
87
morphology of apoptosis
cells shrink
chromatin condensation
cytoplasmic blebs (Cytoplasm breaks up)
macrophages come to revoke debris
88
define neoplasia
new growth not in response to stimulus
89
what is the only body part that has never been reported to undergo neoplastic change
lens of the eye
90
what is metaplasia
reversible change from one mature cell type of another mature cell type
91
what type of metaplasia is often found in response to injury or exposure to noxious stimuli
squamous metaplasia
92
example of metaplasia in the lung
pseudo stratified ciliated epithelium is exposed thermal/chemical injury (smoking) resulting in squamous metaplasia
93
example of metaplasia in the bladder
transitional epithelium is exposed to inflammation (catheter) resulting in squamous metaplasia
94
metaplastic tissue is at risk of
development of cancer
95
what is autonomous hyperplasia
no longer needs stimulus to occur
96
what is dysplasia
abnormal growth not in response to a stimulus
97
define invasion
growth beyond the basement membrane
98
what is carcinoma in situ
dysplasia affecting the whole of the epithelium but does not go beyond the basement membrane
99
what is. the commonest cancer in men
prostate
100
what is the commonest cancer in women
breast
101
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
```
102
which mutation is diagnostic in burkitt lymphoma
t(8:14)
103
how does Bcl-2 prevent apoptosis
binds to bax/bak to stop mitchondria become permeable (doesn't release capsases)
104
what is VEGF
vascular endothelial growth factor
105
an encapsulated lesion implies that it is slow/fast growing
slow
106
carcinomas arise from
epithelium
107
adenoma/adenocarcinoma arise from
glandular tissue
108
squamous epithelium can produce what types of tumour
papilloma
| SCC
109
tumours of connective tissues are called
sarcomas
110
benign tumour of fat
lipoma
111
benign tumour of bone
osteoma
112
malignant cancer of bone
osteosarcoma
113
benign cartilage tumour
enchondroma
114
malignant cartilage tumour
chondrosarcoma
115
define ephelis, naevus, and melanoma
freckle
mole
malignant melanocytic tumour
116
stage vs grade
stage - how much its grown
| grade - how differentiated it is
117
which cancers often present early
```
vocal cords (voice change)
skin cancers (if you can see them)
breast cancer (self-examine)
testicular cancer (self-examine)
```
118
weight loss in cancer is known as
cachexia
119
risk factors for atheroma
```
smoking
HTN
hyperlipidaemia
DM
age
sex (males)
genetics
```
120
where does atheroma occur
sites of turbulent blood flow
| normally branching sites
121
HDL and LDL: good or bad
HDL good
| LDL bad
122
how does atheroma occur
primary endothelial injury
accumulation of lipids and macrophages
digestion of smooth muscle cells over 'foamy' macrophages
increase in size
123
deposition of smooth muscle changes lesion from fatty streak to
fibrofatty plaque
124
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
125
what are complications of atheroma
stenosis
aneurysm
dissection
thrombosis and embolism
126
what is arterial stenosis
narrowing of the arterial lumen
| reduced elasticity and flow
127
arterial stenosis can cause
tissue ischaemia
128
clinical effects of cardiac ischaemia
```
reduced exercise tolerance
angina
unstable angina
MI
cardiac failure
```
129
what is cardiac fibrosis
loss of cardiac myocytes and replacement by fibrous tissue
130
what are the consequences of cardiac fibrosis
loss of contractility
| reduced elasticity and filling
131
arterial stenosis affecting the carotid arteries may cause
TIA
stroke
vascular dementia
132
arterial stenosis affecting the renal arteries might cause
hypertension and renal failure
133
arterial stenosis affecting the peripheral arteries may cause
claudication
| foot/leg ischaemia
134
define aneurysm
abnormal and persistent dilatation of an artery due to a weakness in its wall
135
where is the commonest site of aneurysm formation
abdominal aorta
136
what are complications or aneurysm
```
rupture
thrombosis
embolism
pressure erosion of adjacent structures
infection
```
137
what is an arterial dissection
splitting within the media by flowing blood resulting in false lumen filled with blood within the media
