Introduction To Clinical Sciences Flashcards
1
Q
What is inflammation?
A
- local response to cellular injury
- capillary dilation, leukocytic infiltration, redness, heat, pain
- serves to initiate elimination of noxious agents and damaged tissue
2
Q
When is inflammation good / bad?
A
Good - infection & injury
Bad - autoimmunity / over-reaction to stimulus
3
Q
What causes acute inflammation?
A
Tissue damage (e.g. by noxious compounds, trauma, microbial invasion).
4
Q
Which cells are predominantly involved in acute inflammation?
A
Neutrophils
5
Q
Features of acute inflammation?
A
- sudden onset
- short duration
- usually resolves
6
Q
What causes chronic inflammation?
A
- some viral infections
- hypersensitivity reactions
- persistent causal agent
- sometimes resolution of acute inflammation results in tissue fibrosis & ongoing damage
7
Q
Which cells are predominantly involved in chronic inflammation?
A
Macrophages and lymphocytes
8
Q
Features of chronic inflammation?
A
- slow onset / sequel to acute
- long duration
- may never resolve
9
Q
Lifespan of neutrophils?
A
Short lived, usually die at scene of inflammation (pus).
10
Q
What is the role of lymphocytes in inflammation?
A
- first responders to acute inflammation (respond to agent causing tissue damage)
- have cytoplasmic granules containing bacteria-killing enzymes
- release chemicals to attract other inflammatory cells (e.g. macrophages)
11
Q
Lifespan of macrophages?
A
Weeks - months
12
Q
What is the role of macrophages in inflammation?
A
- phagocytosis of bacteria and debris
- carry debris away
- present antigens to lymphocytes
13
Q
Lifespan of lymphocytes?
A
Years
14
Q
Role of lymphocytes in inflammation?
A
- produce chemicals to attract other inflammatory cells
- immunological memory for past infections
15
Q
What is the role of endothelial cells in inflammation?
A
- become sticky in areas of inflammation so inflammatory cells adhere to them
- become porous to allow passage of inflammatory cells into tissues
- grow into areas of damage to form new capillaries
16
Q
How do capillaries dilate in acute inflammation?
A
Arteriole dilates and precapillary sphincter opens, allowing capillaries to fill.
17
Q
What happens if capillaries all dilate at once?
A
Haemodynamic shock - blood pressure falls rapidly. Occurs in sepsis, for example.
18
Q
What is the role of fibroblasts in inflammation?
A
Long lived, spindle shaped cells.
Form collagen in areas of chronic inflammation and repair.
19
Q
What is a granuloma?
A
An aggregation of immune cells seen in some conditions involving inflammation.
20
Q
When might a granuloma form?
A
- TB
- leprosy
- Crohn’s disease
21
Q
How do antihistamines treat inflammation?
A
Block histamine, a mediator of inflammation.
22
Q
How do corticosteroids treat inflammation?
A
Interact with DNA to suppress inflammatory genes - interact with the transcription complex.
23
Q
How does ibuprofen treat inflammation?
A
Inhibits prostaglandin synthetase, therefore inhibiting prostaglandin synthesis. Prostaglandins are mediators of inflammation.
24
Q
When is damage resolved vs repaired?
A
Resolution - when initiating factor removed, tissue is undamaged or able to regenerate.
Repair - when initiating factor is still present, or tissue is damaged and unable to regenerate.
25
Which cell populations can regenerate?
Labile and stable cells.
26
What is meant by organisation in tissue repair?
- repair of specialised tissue by the formation of a fibrous scar
- dead tissue is removed by phagocytosis and granulation tissue is produced on a fibrin scaffold
- granulation tissue accumulates collagen and the scar forms
27
What does granulation tissue consist of?
Capillary loops and myofibroblasts.
28
What is the role of myofibroblasts in organisation?
They contract to bring surrounding tissues together.
29
What can be a damaging effect of scar contraction in organisation?
May result in a stricture, causing stenosis or obstruction of a lumen.
May result in a muscle contracture.
30
What happens in the event of persistent liver damage?
Liver cirrhosis, then fibrosis.
31
Why is resolution of an abrasion possible (in most cases)?
The bottom skin layer remains so the epidermis can regenerate.
32
What is healing by 1st intention?
- skin edges are close
- a weak fibrin join forms between them
- fibrin join is replaced by a strong collagen join
33
What is healing by 2nd intention?
- gaping loss of tissue
- organisation: granulation tissue fills gap to provide a framework for epithelial cells, then collagen accumulates in it
- epithelial cells grow over the top of the gap
- contraction of fibrous (collagen) scar
34
Which cells produce collagen (e.g. when it accumulates in granulation tissue / in fibrosis)?
Fibroblasts
35
What does gliosis mean?
Fibrosis occurring in the brain.
36
Which cell types can regenerate?
- hepatocytes
- pneumocytes
- all blood cells
- gut and skin epithelium
- osteocytes
37
Which cell types don’t regenerate?
- myocardial cells
| - central neurones (peripheral can repair but rarely regain full functionality)
38
What is meant by laminar flow?
Normal blood flow through the middle of the vessel.
39
Why does endothelial cell injury result in platelet aggregation?
Collagen is exposed which causes platelet adherence & aggregation.
40
What are the features of platelets?
- no nucleus
- alpha granules (involved in platelet adhesion)
- dense granules (involved in platelet aggregation)
- derived from megakaryocytes in bone marrow
41
What is a thrombus formed from?
Layers of aggregated platelets and red blood cells within a fibrin mesh framework.
42
What is meant by thrombosis?
A solid mass of blood constituents formed within an intact vascular system (during life).
43
What are the three components of Virchow’s triad?
- change in the vessel wall (e.g. endothelial injury)
- change in blood flow (e.g. stasis, turbulence)
- change in blood constituents (causing hypercoaguability)
44
Which components of Virchow’s triad are involved when an atheroma forms?
- change in blood flow (turbulence)
| - change in vessel wall
45
What is the most common cause of arterial thrombosis?
Atheroma
46
What is the most common cause of venous thrombosis?
Stasis (most thrombi begin at valves where there is turbulence).
47
What are the 4 possible outcomes for a thrombus?
1) degradation = resolution
2) organisation into a scar (may narrow vessel lumen)
3) recanalisation - when capillaries grow into the thrombus and fuse to form larger vessels, vessel becomes patent again
4) embolism
48
Why is aspirin used to prevent thrombus formation?
Aspirin inhibits platelet aggregation.
49
What is an embolus?
Mass of material in the vascular system, able to become lodged within a vessel and block it.
50
What is the most common form of embolism?
Pulmonary embolism due to deep vein thrombosis.
51
What is a systemic embolus?
An embolus which arises in the arterial system. E.g. from the heart due to AF, or from an arterial atheroma.
52
What is meant by gangrene?
An infarction of mixed tissues in bulk (e.g. part of a limb).
53
Examples of organs with dual blood supply?
- lungs
- liver
- some parts of brain
54
What is meant by shock?
Profound circulatory failure causing hypoperfusion of organs.
55
What are the two types of shock?
Cardiogenic: reduced stroke volume as a result of an acute MI.
Hypovolaemic: loss of effective circulating blood volume.
56
What are the clinical effects of arterial thrombosis?
- loss of pulses distal to thrombus
- area is cold, pale, painful
- tissue death = gangrene
57
What are the clinical effects of venous thrombosis?
- 95% of the time it occurs in leg veins
| - area is tender, swollen and reddened
58
Why doesn’t atherosclerosis occur in pulmonary arteries?
They are a low pressure system so there is no endothelial damage from shearing forces.
59
Why is atherosclerosis common in the aorta and systemic arteries?
High pressure system so the endothelium is subject to shearing forces (particularly at branching points).
60
Examples of agents causing endothelial damage?
- free radicals
- nicotine
- carbon monoxide
61
What is the result of haemorrhage within an atherosclerotic plaque?
Causes plaque expansion.
62
What is meant by elastic and muscular arteries?
Elastic - most major arteries surrounding the heart.
| Muscular - continue from elastic arteries, distributing blood to regions of the body.
63
What is the structure of the artery wall?
Tunica intima: endothelial cells with subendothelium of connective and elastic tissue.
Tunica media:
- elastic arteries: 40-70 fenestrated elastic membranes with smooth muscle cells and collagen between them.
- muscular arteries: ~40 layers of smooth muscle, connected by gap junctions.
Tunica adventitia: connective tissue containing lymphatics, nerves, and vasa vasorum.
64
What are the vasa vasorum?
Blood vessels which supply arteries.
65
What is the structure of an arteriole?
- 3 layers of smooth muscle cells
- no internal elastic lamina
- external elastic lamina present in larger arterioles only
66
What are metarterioles?
- supply capillary beds
- have precapillary sphincters (rings of smooth muscle) to control blood flow to the capillary bed
- no continuous smooth muscle layer (just endothelium)
67
What is the early development stage of an atherosclerotic plaque?
Fatty streak lesion.
- yellow elevation of intimal liming
- composed of lipid-laden macrophages
68
What is the composition of an atherosclerotic plaque?
- central lipid core
- cap of fibrous tissue covered by endothelium
- fibrous cap contains collagen and inflammatory cells
- foam cells present (macrophages what have phagocytosis lipoproteins)
- plaque beck was calcified in later stages
69
What are some risk factors for atherosclerosis?
- hypercholesterolaemia
- smoking
- hypertension
- poorly controlled diabetes
- male
- increasing age
- obesity
- sedentary lifestyle
- low socioeconomic status
- some infections (e.g. influenza)
70
How might certain infections contribute to atherosclerosis?
By switching on inflammation pathways.
71
What main stages are involved in plaque development?
Chronic occurrence of:
1) endothelial injury
2) tissue response of vascular wall to injury (inflammation and repair)
72
What is the cellular response to endothelial injury?
- endothelial cells have increased thrombogenicity, enhanced expression of adhesion molecules for monocytes and increased permeability to LDLs.
X
- thrombus forms, and inflammatory cells and lipids enter the intima and form plaques.
- macrophages and T lymphocytes also accumulate in plaque tissue.
- foam cells die and deposit lipid into the plaque core
73
How do tissue repair processes assist plaque formation?
- growth factors stimulate proliferation of smooth muscle cells
- smooth muscle cells produce collagen to enclose the lipid core in a fibrous cap
74
What are 4 potential clinical manifestations of atherosclerosis?
1) reversible tissue ischaemia (when 50-75% vessel stenosis has occured)
2) acute atherothrombotic occlusion due to plaque rupture
3) embolism (may lead to infarction)
4) ruptured abdominal atherosclerotic aneurysm
75
Which risk factors for atherosclerosis are non-modifiable?
- age
- gender
- family history (genetics & shared environment)
- ethnicity (South Asian / sub-Saharan African - increased risk compared to European)
76
Which risk factors for atherosclerosis are modifiable?
- smoking
- hyperlipidaemia
- sedentary lifestyle
- unhealthy diet
- obesity
- excessive alcohol
77
What are some examples of co-morbidities which have an increased risk of atherosclerosis?
- hypertension
- diabetes (poorly controlled)
- CKD
- dyslipidaemia
- atrial fibrillation
- systemic inflammatory disorders (e.g. rheumatoid arthritis)
- influenza
78
What is meant by apoptosis?
Programmed cell death - individual cell deletion in physiological growth control and in disease.
79
What can happen if apoptosis is reduced?
Neoplasia
80
What can happen if apoptosis is increased?
Atrophy
81
What happens during apoptosis?
- enzymatic digestion of the nucleus and cytoplasmic contents
- phagocytosis of breakdown products (contained in membrane-bound bodies) by neighbouring cells
82
What are some inducers of apoptosis?
- growth factor withdrawal
- loss of matrix attachment
- glucocorticoids
- some viruses
- free radicals
- ionising radiation
- DNA damage
- ligand binding at ‘death receptors’
83
What are some inhibitors of apoptosis?
- growth factors
- extracellular matrix
- sex steroids
- some viral proteins
84
What pathway leads to apoptosis?
Activation of caspases (by the Bcl2 protein, or by the binding of the Fas ligand to the Fas receptor).
85
What is the role of apoptosis in HIV
The HIV virus induced apoptosis in T lymphocytes.
86
What is meant by necrosis?
Traumatic cell death - death of tissues following bioenergetic failure and loss of plasma membrane integrity. Induces inflammation and repair.
87
What is coagulative necrosis?
Most common form of necrosis. Cells retain their outlines so tissue texture is initially normal / firm, and then layer may become soft.
88
What is liquifactive necrosis?
When necrotic tissue liquefies (e.g. cerebral necrosis).
89
What is caseous necrosis?
Seen in TB - where the dead tissue is structureless.
90
What is gangrene? (In terms of necrosis).
Necrosis with putrefaction (decay) of tissues (due to bacteria).
91
What is fat necrosis?
Trauma to adipose tissue, leading to an inflammatory response (fat phagocytosis) resulting in fibrosis.
92
What are homeobox genes?
Genes that regulate gene expression and control aspects of morphogenesis and differentiation.
93
What does congenital mean?
Present at birth (condition may be inherited or acquired during embryogenesis).
94
What are the three most common chromosomal abnormalities?
- trisomy 21 (Down’s syndrome) 1 in 1000 births
- trisomy 18 (Edwards’ syndrome) 1 in 5000 births
- trisomy 13 (Patau’s syndrome) 1 in 6000 births
95
Why does Alzheimer’s occur in people with Down’s syndrome?
Increased beta amyloid deposition in the brain - gene for beta amyloid is located on chromosome 21.
96
What are the three categories of single gene disorder?
- enzyme defects
- defects in receptors or cellular transport
- non-enzyme protein defects
97
What is meant by polygenic inheritance?
Multiple genes involved.
98
What is the difference between acromegaly and gigantism?
Acromegaly is caused by growth hormone excess post-puberty. Causes abnormally large hands and feet, etc.
Gigantism is caused by growth hormone excess pre-puberty. Causes tall stature.
99
What are three types of foetal development anomaly? Examples?
Embryo division abnormalities: e.g. conjoined twins.
Teratogen exposure: e.g. thalidomide
Failure of cell and organ migration: e.g. undescended testis
100
What are 6 anomalies of organogenesis?
- agenesis/aplasia: organ fails to develop
- atresia: lumen fails to develop
- hypoplasia: organ fails to develop its normal size
- maldifferentiation
- ectopia & heterotopia: small areas of mature tissue from one organ are present within another tissue.
- choristoma: one or more mature differentiated tissues aggregate as a tumour-like mass at an inappropriate site.
101
What is hypertrophy?
An increase in the size of a tissue caused by an increase in the size of the constituent cells.
E.g. skeletal muscle
102
What happens in cardiac hypertrophy?
- after an MI, scar tissue replaces myocardial tissue.
- the remaining myocardium undergoes compensatory hypertrophy
- therefore right ventricular hypertrophy may result from left ventricular failure, leading to pulmonary hypertension
103
What is hyperplasia?
Increase in the size of a tissue, caused by an increase in the number of the constituent cells.
E.g. in individuals living at high altitude, hyperplasia occurs in red blood cell-producing bone marrow cells (stimulated by erythropoietin).
104
What causes an enlarged prostate?
Hyperplasia of smooth muscle.
105
How does hyperplasia aid tissue repair?
- proliferation of capillary endothelial cells (angiogenesis) and myofibroblasts in scar tissue.
- regeneration of specialised cells within a tissue.
106
What is meant by atrophy?
Decrease in tissue size caused by a decrease in the number of the constituent cells, or a decrease in their size.
107
What is an example of physiological atrophy?
Involution of Wollfian / Müllerian ducts.
108
What are 7 causes of pathological atrophy?
- decreased function & disuse
- loss of innervation
- loss of blood supply
- pressure atrophy
- lack of nutrition
- loss of endocrine stimulation
- hormone-induced atrophy
109
What is meant by metaplasia?
When a cell changes from one fully-differentiated type to another, due to an altered cellular environment.
110
What types of cells does metaplasia affect?
Epithelial and mesenchymal cells.
| E.g. ciliated columnar epithelium in bronchi becomes squamous as a result of smoking.
111
What can metaplasia give rise to?
Dysplasia and carcinoma.
112
What is meant by dysplasia?
Morphological changes seen in cells in the progression to becoming cancer.
113
What is the difference between metaplasia and dysplasia?
Metaplastic cells have normal architecture and arrangement, whereas this is abnormal in dysplastic cells.
114
What is meant by senescence?
The process by which cells irreversibly stop dividing and enter a state of permanent growth arrest without undergoing apoptosis.
115
What is meant by frailty syndrome?
A gradual deterioration in health, leading to death (where there is no single cause / combination of causes).
116
What are some characteristics of frailty syndrome?
- sarcopenia
- reduced activity
- poor appetite
- osteoporosis
- frequent falls
117
What is the role of the telomere of a chromosome?
Telomere shortens with every cell division, limiting the number of mitotic divisions that a cell can perform.
118
What are some causes of ageing and death in cells, other than telomere shortening?
- cross-linking or mutations of DNA
- loss of calcium influx controls
- damage to mitochondrial DNA
- loss of DNA repair mechanism
- free radicals generation
- accumulation of toxic by-products of metabolism
- activation of ageing and death genes
119
What causes dermal elastosis in old age?
Exposure to UV-B light causes protein cross-linking. Therefore the skin contains less collagen and elastin, and the remainder is abnormal.
120
Why is immunity impaired in old age?
- increased memory cells but decreased naive cells, so reduced capacity to respond to novel antigens.
- thymus (source of T cells) atrophies.
121
What implications does impaired immunity have in old age?
- recurrence of dormant previous infections (e.g. chicken pox virus as shingles).
122
What cardiovascular changes are seen in old age?
- accumulated atherosclerotic lesions
| - loss of elasticity in arteries = increased systolic BP
123
What is osteoporosis? What implications does it have?
Loss of bone matrix (normal mineralisation but thinned trabeculae) due to increased bone resorption and decreased bone formation. Linked to a lack of oestrogen.
Causes fractures of vertebral bodies, leading to stooped posture and loss of height. Increased risk of fragility fractures.
124
What causes cataracts?
Exposure to UV-B light causes protein cross-linking, damaging the lens.
125
What is meant by sarcopenia? Why does it occur?
Loss of muscle due to decreased growth hormone, decreased testosterone, and increased catabolic cytokines.
126
What causes deafness in old age?
Loss of hair cells in the cochlea.
127
Does basal cell carcinoma metastasise?
No, it only invades locally (but it is malignant).
128
How is basal cell carcinoma treated?
Complete local excision. Skin graft may be required for healing.
129
Where do carcinomas commonly spread?
To lymph nodes draining the site of the carcinoma.
130
Lymph nodes where breast cancer spreads to?
Axillary lymph nodes.
131
Which cancers commonly spread to bone?
- breast
- prostate
- lung
- thyroid
- kidney
132
How is a breast cancer diagnosis confirmed?
- mammogram & ultrasound scan
| - biopsy
133
How is it determined whether breast cancer has spread to the axilla?
Biopsy of lymph nodes / scan.
134
How is it determined whether breast cancer has metastasised?
- bone scan
| - CT scan (e.g. liver)
135
Why can a tumour reoccur if it has been completely excised?
Micro metastases could be present.
136
What is adjuvant therapy?
Extra treatment given after surgical excision of a tumour (e.g. chemotherapy, radiotherapy) to destroy micro metastases.
137
What crystals are deposited in tissues in gout?
Uric acid crystals.
138
What is calcification in diseased tissues called?
Dystrophic calcification.
139
How does vinblastine work?
Antimicrotubule agent so inhibits metaphase.
140
How does etoposide work?
Inhibits topoisomerase (unwinds DNA helix) so inhibits DNA replication.
141
How does ifosamide work?
Binds directly to DNA causing cross-linking, inhibits DNA synthesis.
142
How does cisplatin work?
Binds directly to DNA, causing cross linking. Inhibits DNA synthesis.
143
What are the drawbacks of conventional chemotherapy?
```
Not selective for tumour cells.
Damages healthy dividing cells, causing:
- myelosuppression (damages bone marrow cells, resulting in low white blood cell count and anaemia).
- hair loss
- diarrhoea
```
144
What is choriocarcinoma?
Malignant tumour of the placenta.
145
How are differences between cancer cells and healthy cells studied?
- gene arrays
- proteomics
- tissue microarrays
146
Which alterations to growth factor receptors might appear in tumour cells?
- over-expression = more cell proliferation
| - constitutive activation of receptor (always switched on) = more cell proliferation
147
How can alterations to growth factor receptors be exploited in targeted cancer therapy?
- monoclonal antibody against growth factor receptor
| - small molecular inhibitor of growth factor receptor
148
How does cetuximab work?
Monoclonal antibody binds competitively to external domain of EGFR.
149
What is EGFR?
epidermal growth factor receptor
150
How are patients selected for Cetuximab therapy?
Immunohistochemistry - stain for EGFR.
151
How does herceptin work?
Monoclonal antibody against Her-2 (human epidermal growth factor receptor 2).
Promotes endocytosis of Her-2.
Flags cancer cells for lymphocyte recognition.
152
What is the her-2 gene associated with in terms of breast cancer characteristic?
- large size
- high grade
- aneuploidy
- negative oestrogen receptor status
- poor prognosis
153
How is her-2 amplification detected?
- fluorescent in situ hybridisation (FISH)
| - immunohistochemistry
154
What is meant by carcinoma in situ?
An epithelial neoplasm exhibiting all the cellular features associated with malignancy, but which has not yet invaded through the epithelial basement membrane separating it from potential routes of metastasis.
155
What is meant by micro-invasive carcinoma?
Carcinoma has invaded through the basement membrane but has not spread far. There is a low chance of metastasis and it can still be treated locally.
156
How do neoplastic cells invade the basement membrane?
- cell motility (due to gene activation)
| - proteases - matrix metalloproteinases
157
How do neoplastic cells invade the extracellular matrix?
- cell motility
| - proteases - matrix metalloproteinases
158
How do tumour cells become motile?
Motility factors:
- tumour cell derived motility factors
- breakdown products of extracellular matrix
159
What is the name for the process by which tumour cells invade the capillary endothelium? How do tumour cells achieve this?
Intravasation
- collagenases
- cell motility
160
How do tumour cells evade the host immune defence in the blood stream?
- aggregation with platelets
- shedding of surface antigens
- adhesion to other tumour cells
161
How do neoplastic cells leave blood vessels and enter tissues? What is the name for this process?
Extravasation
- adhesion receptors
- collagenases
- cell motility
162
How does the neoplasm develop at the metastatic site?
- growth factors (often neoplastic cells produce their own)
| - angiogenesis promotors: e.g. vascular endothelial growth factor (VEGF)
163
How does avastin inhibit angiogenesis? What is its current use?
- binds to VEGF, stopping it from binding to its receptor
| - was ineffective in cancer trials, but has a use in treating wet macular degeneration
164
Which tumours commonly metastasise to the liver?
- colon
- stomach
- pancreas
- neuroendocrine (carcinoid) tumours of the small intestine
165
How do metastases reach the liver?
Via the portal circulation.
166
What are the two types of bone metastasis?
Lytic - causes bone breakdown.
| Sclerotic - causes new bone formation.
167
What is the definition of neoplasm?
A lesion resulting from the autonomous (or relatively autonomous) growth of cells, which persists after the initiating stimulus has been removed.
168
3 most common cancers in males?
- prostate
- lung
- bowel
169
3 most common cancers in females?
- breast
- lung
- bowel
170
True or false: neoplastic cells can derive from non-nucleated cells (e.g. red blood cells).
False: they derive from nucleated cells only.
171
True or false: neoplastic cells are usually monoclonal.
True
172
What is the neoplastic stroma?
- connective tissue framework
| - provides mechanical support and nutrition
173
What cells and tissue types are found in the neoplastic stroma?
- fibroblasts (produce collagen)
| - blood vessels
174
What is meant by a benign neoplasm?
A localised, non-invasive neoplasm.
175
Growth rate and mitotic activity of a benign neoplasm?
- slow growth
| - low mitotic activity
176
Does a benign neoplasm resemble normal tissue?
Close resemblance.
177
How are benign neoplasms localised?
They are circumscribed or encapsulated.
178
What is the nuclear morphometry of a benign neoplasm?
Often normal.
179
Does necrosis / ulceration often occur in a benign neoplasm?
Necrosis and ulceration are rare because benign neoplasms don’t usually outgrow their blood supply.
180
Are benign neoplasms exophytic or endophytic?
Exophytic - they can’t invade underlying tissues so grow upwards and outwards.
181
How do benign neoplasms cause morbidity and mortality?
- pressure on adjacent structures
- obstruct flow
- production of hormones
- become a malignant neoplasm
- cause anxiety
182
What is meant by a malignant neoplasm?
Malignant neoplasms are invasive and commonly metastasise.
183
What is the growth rate and mitotic index for a malignant neoplasm?
- rapid growth rate
| - high mitotic index
184
Does a malignant neoplasm resemble normal tissue?
Variable resemblance:
- good resemblance (well-differentiated) = low grade
- poor resemblance (poorly-differentiated) = high grade
185
What characteristics do nuclei have in malignant neoplasms?
- hyperchromatic nuclei
| - pleomorphic nuclei
186
Does necrosis / ulceration occur in malignant neoplasms?
Necrosis and ulceration is common as the neoplasm often outgrows its blood supply.
187
Is the growth of a malignant neoplasm exophytic or endophytic?
Often endophytic due to invasion of underlying tissues.
188
Morbidity and mortality caused by malignant neoplasms?
- destruction of adjacent tissue
- metastases
- blood loss from ulcers
- obstruction of flow
- hormone production
- paraneoplastic effects
- anxiety and pain
189
What is meant by paraneoplastic effects?
Metabolic effects due to tumour secretion of chemical signalling molecules, or the immune response to the tumour.
190
What is a papilloma?
Benign tumour of non-glandular, non-secretory epithelium.
191
What is an adenoma?
Benign tumour of glandular or secretory epithelium.
192
What is a carcinoma?
Malignant epithelial neoplasm.
193
What is an adenocarcinoma?
Malignant tumour of glandular epithelium.
194
What is a lipoma?
Benign neoplasm from adipocytes.
195
What is a chondroma?
Benign neoplasm from cartilage.
196
What is an osteoma?
Benign neoplasm from bone.
197
What is an angioma?
Benign vascular neoplasm.
198
What is a rhabdomyoma?
Benign neoplasm of striated muscle.
199
What is a leiomyoma?
Benign neoplasm of smooth muscle.
200
What is a neuroma?
Benign neoplasm from nerves.
201
How are malignant connective tissue neoplasms named?
‘sarcoma’ prefixed by cell type of origin:
- liposarcoma
- rhabdomyosarcoma
- osteosarcoma
202
What is meant by an anaplastic tumour?
A tumour where the cell-type of origin is unknown - malignant with a poor prognosis.
203
What is a melanoma?
Malignant neoplasm of melanocytes.
204
What is a mesothelioma?
Malignant neoplasm of mesothelial cells (e.g. pleura).
205
What is a lymphoma?
Malignant neoplasm of lymphoid cells.
206
What is a leukaemia?
Malignant neoplasm of haemopoeitic organs.
207
What is a teratoma?
Neoplasm containing elements of each layer of the trilaminar disk.
208
Where do teratomas occur most often?
The gonads, where germ cells are abundant.
209
What is a blastoma?
Neoplasm with a histological resemblance to the embryonic form of the organ in which they arise.
210
What is meant by a mixed tumour?
Tumour consisting of a combination of cell types.
211
What is meant by an endocrine tumour?
Tumour consisting of peptide hormone-secreting cells in epithelial tissues, often functionally active.
212
What is meant by a carcinoid tumour?
An endocrine tumour that doesn’t produce any known peptide hormones, or produces a mixture of peptide hormones.
213
What is meant by a carcinosarcoma?
A mixture of carcinoma and sarcoma, malignant.
214
What is a hamartoma?
A benign tumour-like lesion. Consists of two or more mature cell types normally found in the organ in which it arises. Growth of a hamartoma is related to overall body growth. May be mistaken for a malignant neoplasm.
215
What is a cyst?
Fluid-filled space lined by epithelium. Some are neoplasms, some aren’t - may have local effects similar to those produced by the true tumour.
216
What are some challenges when trying to identify carcinogens?
- latent interval may be decades
- environment is complex
- ethical constraints
217
Where is hepatocellular carcinoma common?
- areas with hepatitis B/C
| - areas with mycotoxins
218
What types of laboratory evidence for carcinogens are there?
- incidence of tumours in laboratory animals
- cell/tissue cultures
- mutagenicity testing in bacterial cultures
219
What are the drawbacks to laboratory evidence for carcinogens?
- animals / cultures may metabolise agents differently to humans
- bacterial mutation may not = carcinogenicity
220
What is meant by a pro-carcinogen?
A chemical carcinogen that requires metabolic conversion to become an ultimate carcinogen.
221
What cancers can polycyclic aromatic hydrocarbons causes?
- lung cancer
| - skin cancer
222
What are two sources of polycyclic aromatic hydrocarbons?
- smoking
| - mineral oils
223
What type of cancer can aromatic amines cause?
Bladder cancer
224
Which occupation(s) involve contact with aromatic amines?
Rubber / dye workers
225
Which cancers are associated with alcohol?
- oropharynx
- larynx
- oesophagus
- liver
- breast
- colorectal
226
What are the processes by which alcohol causes cancer?
- ethanol affects mucous membranes, making it easier for cells in the oropharynx to absorb other carcinogens
- ethanol increases oestrogen levels
- acetaldehyde (metabolite of ethanol) is a mutagen
227
Which disease is caused by the Epstein-Barr virus?
Infectious mononucleosis (glandular fever).
228
Which cancers can be caused by the Epstein-Barr virus?
- nasopharyngeal carcinoma
- Burkitt’s lymphoma
- Hodgkin’s lymphoma
- B- and T-cell lymphomas
- leiomyosarcoma
229
Which cancers can be caused by HPV?
Squamous cell carcinomas of the:
- oropharynx
- cervix
- vulva
- vagina
- penis
- anus
230
Which cancer can be caused by the hep B virus?
Hepatocellular carcinoma
231
Which cancers can be caused by human herpes virus 8?
- Kaposi’s sarcoma
| - primary effusion lymphoma
232
What is a primary effusion lymphoma?
An HIV-associated lymphoma that arises in body cavities such as the pleural space, pericardium and peritoneum.
233
Which cancers can be caused by human T lymphotrophic virus 1?
Adult T-cell leukaemia / lymphoma
234
Which cancers can be caused by the hep C virus?
- hepatocellular carcinoma
- non-Hodgkin’s lymphoma
- potentially pancreatic cancer and cholangiocarcinoma (bile duct cancer)
235
Which cancers can be caused by exposure to UV light?
- basal cell carcinoma
- melanoma
- squamous cell carcinoma
236
Which condition increases risk of cancer due to UV light exposure?
Xeroderma pigmentosum - extreme sensitivity to UV light.
237
Which cancers are associated with increased oestrogen levels?
- breast cancer
| - endometrial cancer (type of uterine cancer)
238
Which cancer is associated with anabolic steroid use?
Hepatocellular carcinoma
239
What is an example of a mycotoxin and it’s associated cancer?
Aflatoxin B (found in contaminated food) - hepatocellular carcinoma
240
What is cholangiocarcinoma?
Bile duct cancer
241
What are two examples of cancers that can be caused by parasites?
- cholangiocarcinoma: can be caused by chlonorchis sinesis, a parasite that lives within bile ducts
- bladder cancer: can be caused by shistosoma
242
Which cancers can asbestos cause?
- mesothelioma
- lung cancer
- laryngeal cancer
- ovarian cancer
243
What is a premalignant condition?
Local abnormality associated with increased risk of malignancy at that site.
244
What are some examples of premalignant conditions?
- colonic polyps
- cervical dysplasia
- ulcerative colitis
- undescended testis
245
What are the three main stages in the process of carcinogenesis?
Initiation - carcinogen induces genetic alterations that give the cell its neoplastic potential.
Promotion - stimulation of clinal proliferation of the initiated cell.
Progression - process leading to malignant behaviour.
246
What genetic alterations are needed for a cell to become neoplastic?
- expression of telomerase
- inactivation of both copies of a tumour suppressor gene
- activation of oncogenes
247
What causes increased genomic instability?
- ageing
| - some genetic conditions
248
What are the two types of tumour suppressor gene?
Caretaker genes: repair DNA damage
| Gatekeeper genes: stop proliferation of cells with DNA damage
249
Where is the p53 gene located?
p arm of chromosome 17
250
What is the function of the p53 gene?
- repairs DNA damage by arresting the cell cycle in G1 until damage is repaired
- stimulates apoptotic cell death if there is extensive DNA damage
251
How can p53 lose its function?
- DNA mutations
- complexes form of normal and mutant p53 proteins (this inactivâtes the normal protein)
- binding of normal p53 protein to proteins encoded by oncogenic DNA viruses (e.g. HPV)
252
What is Li-Fraumeni syndrome?
Inherited germline mutation in the p53 gene (heterozygous).
253
What are the 5 classifications of oncogenes?
- growth factors
- growth factor receptors
- signalling mediator with tyrosine kinase activity
- signalling mediator with nucleotide binding activity (disrupts intracellular signalling)
- nuclear-binding transcription factor onco-proteins (regulate cell proliferation)
254
What is tyrosine kinase?
Enzyme - functions as an ‘on’ or ‘off’ switch in many cellular functions. Transfers a phosphate group from ATP to the tyrosine residues of proteins within a cell.
255
How are oncogenes activated?
- mutation resulting in an excessively active onco protein molecule
- gene amplification / enhanced transcription resulting in excessive oncoprotein production
256
How does epigenetics contribute to genetic alterations in neoplastic cells?
- hypermethylation of promoter DNA sequences = gene silencing
- histone modifications can up- or down-regulate genes (methylation, acetylation, phosphorylation)
- miRNA degrades mRNA, leading to reduced expression
- changes to the number of copies of enhancer and silencer DNA sequences
257
What is the structure of a neoplasm?
- neoplastic cells
| - stroma
258
What is the neoplastic stroma?
Connective tissue framework for mechanical support, intercellular signalling and nutrition.
259
How is the neoplastic stroma formed?
Tumour cells produce growth factors, inducing connective tissue fibroblast proliferation.
260
Why do some cancers have abundant myofibroblasts?
Provide contractility to retract adjacent structures.
261
Example of a factor that limits the growth of a tumour?
Blood supply - the ability of nutrients to diffuse into the neoplastic cells.
262
How is angiogenesis induced?
Factors secreted by tumour cells - e.g. vascular endothelial growth factor (VEGF).
263
Why might some tumours have a lymphocytic infiltrate? What impact does this have on prognosis?
A lymphocytic infiltrate likely reflects a host immune reaction to the tumour. These tumours generally have a better prognosis.
264
What can be seen on histological images of neoplastic cells?
- loss of differentiation
- loss of cellular cohesion
- nuclear enlargement, hyperchromasia & pleomorphism
- increased mitotic activity
265
Which tumour shapes are usually benign?
- sessile
- pedunculated polyp
- papillary
266
Which tumour shapes are usually malignant?
- exophytic / fungating
- ulcerated
- annular
267
Where are annular tumours found?
Common in large bowel, often cause intestinal obstruction.
268
Does sarcoma have an in situ phase?
No, only carcinoma has an in situ phase?
269
What is the route of metastasis in carcinoma vs sarcoma?
Carcinoma - lymph
| Sarcoma - blood
270
How do neoplastic cells achieve proliferation and immortalisation?
- autocrine growth stimulation (expression of oncogenes for growth factors, etc)
- inactivation of tumour suppressor genes
- reduced apoptosis (apoptosis inhibiting genes)
- telomerase
271
What is nuclear hyperchromasia?
More DNA per cell than in the normal population.
272
What is aneuploidy / polyploidy?
Abnormal / increase number of chromosomes. Associated with increased tumour aggressiveness and nuclear pleomorphism.
273
Why might neoplastic cells synthesise unexpected substances?
Some genes are de-repressed in neoplastic cells.
