Pathology (+neoplasia) Flashcards
(109 cards)
1
Q
What is meant by tumour heterogeneity?
A
where a tumour contains multiple cells that have different mutations that each have a selective advantage to evade the immune system/ avoid clearance
2
Q
What is polyploidy?
A
exact multiple of your diploid state
3
Q
what is aneuploidy?
A
inexact multiples of the diploid state
4
Q
What is a carcinogen?
A
mutagenic substances that act on the DNA of cells causing tumours
5
Q
What are HPVs two oncoproteins?
A
E6 and E7
6
Q
What do oncoproteins bind to to suppress cell cycle repair mechanisms?
A
p53
7
Q
What does the E7 viral oncoprotein of HPV cause?
A
tumour suppressor gene that encodes the retinoblastoma protein
8
Q
What does the E6 viral oncoprotein of HPV act on?
A
TP53 preventing it from regulating DNA replication and initiating apoptosis
9
Q
What is the function of retinoblastoma protein and which phase of the cell cycle does it act on?
A
regulates cell cycle progression at the G1-S phase
10
Q
List the six steps of acute inflammation
A
- release of chemical mediators
- vasodilation
- increased vascular permeability (exudation)
- fluid accumulation
- cell recruitment
- phagocytsosis
11
Q
What are the cardinal signs of inflammation?
A
redness
heat
swelling
pain
loss of function
12
Q
what cytokine attracts neutrophils?
A
IL-8
13
Q
neutrophils can undergo movement by rearranging their microtubules, true or false?
A
true
14
Q
Name three types of opsonins from the complement system
A
C4b, C3b and C2a
15
Q
Name three complement derived molecules that can induce chemotaxis of neutrophils
A
C5a, C3a and C567
16
Q
Name the three steps in order for neutrophil migration
A
- margination
- adhesion
- emigration
17
Q
what happens during emigration of neutrophils
A
they pass through the endothelium and through the basal lamina into the adventicia
18
Q
list four chemicals involved in acute inflammation
A
leukotrienes
prostaglandins
serotonin
chemokines
19
Q
what cell produces leukotrienes
A
neutrophils
20
Q
why are prostaglandins involved in acute inflammation
A
they stmulate platlet aggregation
21
Q
what is the process in which soluble fibrinogen is converted into fibrin
A
coagulation
22
Q
what is the fucntion of serotinin in acute inflammation
A
vasconstrictor
23
Q
What are four outcomes of acute inflammation
A
resolution (return to homeostasis)
chronic inflammation
suppuration (formation of ous from dead/dying neutrophils)
scarring/fibrosis tissue
24
Q
what is an example of an inappropriate inflammatory response
A
anaphylaxis - allergic reaction
25
What is healing by secondary intention
where there has been excess tissue damage and loss that that the wound heals from the basal lamina upwards
26
what is granulation tissue made up of
capillaries, collagen and extracellular matrix
27
Name the five stages of bone healing post fracture
haematoma
inflammation
fibrovascular
bone formation
remodelling
28
if there is a loss of hepatocytes in the liver without damage to the architecture, can complete healing occur?
yes
29
What causes acute inflammtion to move into chronic inflammation
| four points
causative agent is not removed
cellular exudate changes
suppurative not resolving
presence of foreign material
30
what cell line does not contain a hayflick limit
| Henrietta Lacks :)))
HeLa
31
What is cellular senescense
cell ages but stops dividing
32
what is the hayflick limit
the number of times a somatic cell population will divide
33
What reduces the hayflick limit as we age
shortening telomeres
34
Why do cells undergo sensensence
| relating to age of the cell
because their telomeres are too short
35
what are telomeres
caps at the end of the chromosome that shorten at each cell division
36
What is werners syndorme
| "Adult progeria"
a mutation in ther WRN gene on chromosome 8 causes accelerated ageing post puberty and the adolescent growth spurt does not occur
37
What is the mutation in down syndrome
trisomy 21
38
What are the symptoms of down syndrome
accelerated ageing and shortened life expectancy
39
Which two proteins can prevent expression of hTERT and reduce/supress telomaerase activity?
RB and p53
40
Why are free radicals not always bad?
neutrophils and macrophages make them to kill pathogens (NADPH complex)
41
What is a detrimental effect of free radicals
causes DNA damage
42
What happens in Xeroderma pigmentosum
sun exposure causes UV damage to DNA and mechanisms of repair deffective to unable to repair the skin damage - can often develop skin cancers
43
What happens to the skin as we age?
less elastin and collagen and atrophy of the dermis
44
what are cardiovascular signs of ageing
elastin:collagen decreases
conduit arteries cannot stretch as much so increased systolic BP
45
What is immunosenensence
| and what immunological fucntions affect this
ageing of the immune system that it does not perform its optimal function - the thymus atrophies so less naiive cells are being generated resulting in more memory cells present
46
what is osteoarticular ageing
osteoporosis - trabeculae are thinned out
47
what is necrosis
cell death that can causes the cell to swell, a disruption to the cell membrane and expulsion of the cell contents
48
What are the four types of necrosis?
coagulative
colliquative
caseuous
fat
49
Where can coagualtive necrosis be found?
heart/kidneys (areas with a rich blood supply) - cell death with some bit of intact-ness
50
Where can you find colliquative necrosis
in the brain (contains pus and liquid)
51
Where can you find caseuous necrosis?
TB
52
Where can you find fat necrosis?
in adipose tissue tends to be a pancreatitis - rupture of fat cells and chalky deposits
53
what is apoptosis
programmed cell death that causes cell shrinking and is contained
54
what happens during the intrinsic pathway of apoptosis
this is a mitochondrial pathway which causes the release of cytochrome C from the mitochondria - cleaves pro caspase 9 into caspase 9 - which cleaves procaspase 3 into active capsase 3 making an apoptosome triggering cell death
55
What are the two extrinsic pathways of apoptosis
TNF and Fas
56
What are the steps of the TNF pathway of apoptosis
TNF receptor activated by TNF - triggers TRADD domain and FADD domain
forms complex with procaspase 8 which cleaves into caspase 8 which then converts procaspase 3 into activated caspase 3 creating the apoptosome and apoptosis
57
What are the steps in the FAS pathway of apoptosis
fas ligand binds to the fas receptor starts a complex of FADD procaspase 8 (death inducing sgnalling complex (DISC)) - cleaving procapspase 3 into active caspase 3 leading to apoptosis
58
Give physiological examples in which apoptosis is used
| 3
embryogenesis (apoptosis of webbed fingers)
elimiination of cells from endometrium during menstrual phase
cancer prevention
59
What is meant by a malignant neoplasm?
neoplasma with potentailly lethal abnormal characteristics that allow it to invade the body and metastasise
60
what is a benign neoplasm
one that does not have the ability to metastatsise and invade the body but in some cases can still be harmful
61
what are the four distinguishing features of a neoplasm
differentiation, local invasion, metastasis and rate of growth
62
anaplastic refers to tumours that are well differentiated, true or false?
false, they are undifferentiated making it difficult to distinguish the tissue of origin
63
are benign tumours usually more or less differentiated?
well-differentiated resembles its tissue of origin
64
what is metaplasia?
change in the phenotype of the cells often in response to chronic irritation
65
what is hypertrophy?
increased cell size often in response to increased work-load
66
what is hyperplasia?
increase in cell number due to a stimulus such as growth factors etc
67
what is a grade 3 tumour
one that is poorly differentiated and hence highly anaplastic some anaplasia
68
what grade is a well-differentiated tumour?
grade 1
69
What are the features of poor differentiation?
| 6 points
abnormal nuclear size and shape
abnormal nuclear features
increased mitotic activty
decreased cell order
necrosis
tumour giant cells
70
What is displasia?
neoplastic change that is confined to the basal membrane
| it can regress so does not always lead to malignancy
71
why is displasia not always malignant?
because it is confined to the basal membrane and only when it breaches this does the tumour become malignant, displasia can also reverse
72
malignant neoplasms are slow growing, true or false?
false
| fast growing (benign are slow growing)
73
what does the border of a benign tumour look like?
encapsulated and contained
| fibrous capsule
74
is carcinoma in situ malignant?
No, it is the highest grade of displasia
75
what is the highest grade of displasia known as
carcinoma in situ
76
what two subsets are epithelial tumours classed into?
surface/ non glandular and glandular
77
breakdown the meaning of an adenoma
aden (glandular) oma (benign)
78
what does a papilloma refer to
benign tumour of a non gladular surface/ epithelium
79
what would a benign tumour of the skin be called?
squamous cell papilloma
80
what is a benign tumour of the glandular epithelium in the colon called?
colonic adenoma
81
benign tumor of the smooth muscle?
leiomyoma
82
what is a chondroma?
benign tumour in the cartilage
83
what is a malignant epithelial tumour called?
carcinoma
84
what is an adenocarcinoma?
malignant tumour of the glandular epithelium
85
what is a sarcoma?
malignant mesenchymal tumour
86
what is a hamartoma?
non-neoplastic disordered overgrowth of normal tissue
87
what is melanocytic naevus?
benign proliferation of melanocytes
88
what is malignancy of melanocytes known as
melanoma
89
define the following
1. lymphoma
2. myeloma
3. leukaemia
1. malignancy of B or T cell origin (hogkins or not)
2. malignancy of the plasma cells
3. malignancy of white blood cells - begins in the bone marrow
90
Name five hallmarks of cancer
avoiding immune destruction
enabling replicative immortality
evading growth suppressors
tumour promoting inflammation
activating invasion and metastasis
genomic instability
inducing angiogenesis
resisiting cell death
deregulating cellular energetics
sustaining proliferative signalling
91
how do neoplastic cells become "immortal"
abnormal expression of oncogenes or innactiavtion of tumour suppressor genes
reduced apoptosis
increased telomerase activity
92
what gene is expressed by tumours that can inhibt apoptosis
BCL-2
93
what is an oncogene?
encodes for an oncoprotein that promotes neoplastic growth of cells (cancer will use this to enhance growth)
94
is p53 an oncogene?
no, it is a tumour-suppressor gene
95
how do we predict for carcinogens?
epidemiological evidence
96
Give an example of a chemical carcinogen
aromatic amines
polycyclic aromatic hydrocarbons (smoking)
nitrosamines (tobacco and cured meats)
azo dyes
vinyl chloride
97
What are the oncogenic viruses?
HPV
Epstein-barr
hep B and C
herpes
human T cell lymphotropic virus
98
What type of tumour can be acquired from coinfection of HPV?
squamous cell carcinoma in the anogenital region
99
How does HPV increase the risk of cancer?
the virus produces two oncoproteins which bind to p53 and RB both of which enhance cell cycle progression
100
What cancer is EBV associated with?
b cell lymphomas and in some cases squamous cell carcinoma
| not much is known about the carcinogenesis
101
which tissues are the most sensitive to ionising radiation?
thyroid (Chernobyl)
bone
breast
haematopoetic tissue
102
What bacteria can be associated with cancer acquisition?
helicoacter pylori (h.pylori)
103
how does h. pylori lead to adenocarcinomas?
secrete toxins that activate oncoproteins
104
What genes can increase susceptibility to breast cancer?
BRCA1 and BRCA2
105
What hormone can be linked to carcinogenesis and how?
oestrogen and via increased production along with growth factors from adipose cells increasing cell proliferation
106
What are the steps in metastasis?
1. detachment
2. invasion of surrounding tissue
3. intravasation into vessels
4. evasion of host defences
5. adherence to endothelium elsewhere
6. extravasation of cells from vessel to surrounding tissue
107
whats transcoelomic metastasis?
when the cancer cells cross a body cavity along the peritoneum
108
Name some examples of oncogenes?
PDGF
ras
src
109
