Pathology- Introduction to Clinical Sciences Flashcards
1
Q
What is atherosclerosis?
A
A disease characterised by the formation of atherosclerotic plaques in the intima of large and medium-sized arteries, e.g. coronary arteries
2
Q
Where does atherosclerosis occur?
A
Only occurs in high-pressure arteries
3
Q
What is visible in atherosclerotic plaques?
A
Lipids- mainly cholesterol
Fibrous Tissue
Lymphocytes
4
Q
Risk factors of atherosclerosis (6)
A
Cigarette smoking
High blood pressure
Diabetes
Hyperlipidaemia
Male sex
Increasing age
5
Q
Complications of atherosclerosis
(6)
A
Cerebral infarction
Carotid atheroma, leading to TIAs
Myocardial Infarction
Aortic aneurysm (can cause sudden death)
Peripheral vascular disease
Gangrene
6
Q
Most important risk factor in atherosclerosis
A
Hypercholesterolaemia
7
Q
Preventative Measures for atherosclerosis (5)
A
Smoking cessation
Blood pressure control
Weight reduction
Low-dose aspirin 🡪 inhibits the aggregation of platelets
Statins 🡪 cholesterol-reducing drug
8
Q
What is apoptosis
A
Programmed cell death
9
Q
Define genetic disease
A
a disease that occurs primarily from a genetic abnormality
10
Q
Define inherited disease
A
caused by an inherited genetic abnormality
11
Q
What is a single gene disorder
A
Abnormality of a single gene causes a disease
12
Q
How can a single gene disorder be classified
A
Dominant
Recessive
Further classified as autosomal or sex-linked.
13
Q
What is an example of a single-gene disorder
How is it caused?
A
sickle cell anaemia
caused by a point mutation in the beta-globin chain of haemoglobin which always produces an abnormal haemoglobin which causes red blood cells to deform when oxygen saturation is low
14
Q
What is a polygenic gene disorder
A
genetic disease which is the result of the interaction of several different genes (usually on different chromosomes)
15
Q
Give an example of a polygenic gene disorder
A
Breast cancer
The genes BRCA1 and BRCA2 have a large individual effect on breast cancer.
Most breast cancer risk is composed of incremental rises in risks by tens to hundreds of apparently unrelated genes, even when there is a strong family history.
16
Q
Define congenital disease
A
A disease someone is born with
17
Q
Congenital diseases will typically be ..
A
genetic
But it can also be acquired (occurs after birth). This disease is often due to environmental factors, but it may have a strong genetic background.
18
Q
Give an example of autosomal recessive disease
A
cystic fibrosis
sickle cell anaemia
19
Q
Classifications of growth & development disorders
A
Congenital
Acquired
Multifactorial disease
20
Q
How is congenital disease further subdivided?
A
Genetic: can be inherited or spontaneous
Non-genetic: e.g environmental
21
Q
Examples of congenital spontaneous genetic disease
A
Down’s syndrome - Trisomy 21; mental retardation, flattened facial profile & short hands
Edwards’ syndrome - Trisomy 18; ear, jaw, cardiac & renal abnormalities
Patau’s syndrome - Trisomy 13; microcephaly, cleft palate & abnormal ears
22
Q
Examples of congenital inherited genetic disease (5)
A
- Cystic fibrosis - autosomal recessive
- Sickle cell anaemia - autosomal recessive
- Familial adenomatous polyposis - autosomal dominant
- Colour blindness - X-linked, men more susceptible
- Huntington’s - present at birth but only manifests later in life
23
Q
Example of non-genetic congenital environmental disease
A
foetal alcohol syndrome
24
Q
Examples of acquired disease
A
- Tuberculosis
- Lung cancer
- Bone fracture
- AIDS
25
What is the response of a cell to increase functional demand?
The response of an individual cell to increased functional demand is to increase tissue or organ size by; hypertrophy, hyperplasia or a combination of both
26
Define hypertrophy
Increase in cell size without cell division
i.e increase in the size of a tissue caused by an increase in the size of the constituent cells
27
Define hyperplasia
increase in the size of a tissue caused by an increase in the number of the constituent cells
28
Define atrophy
decrease in the size of a tissue caused by a decrease in the number of constituent cells or a decrease in their size
-often done by a mechanism called apoptosis
-occurs naturally
29
Define metaplasia
change in differentiation of a cell from one fully-differentiated type to a different fully-differentiated type
30
What describes an adaptive response to injurious stimuli?
Metaplasia
31
Define dysplasia
imprecise term for the morphological changes seen in cells in the progression to becoming cancer
Also refers to a lack of development
32
In what cells does hyperplasia not occur? Why?
Myocardial and nerve cells
As they cannot divide
33
Where does muscle hypertrophy occur?
Skeletal muscle of the limbs (response to increased muscle activity)
Left ventricle (response to sustained outflow resistance)
34
When does hypertrophy of uterine smooth muscle occur
During puberty and pregnancy - stimulated by oestrogens
35
What happens to people living at high altitudes regarding hyperplasia?
Increased production of the growth factor erythropoietin stimulates hyperplasia of bone marrow cells that produce red blood cells in people living at high altitudes
36
Which hyperplasia can either be benign or cancerous
Hyperplasia of prostate smooth muscle
37
When does metaplasia occur?
response to alterations in the cellular environment
38
Examples of metaplasia?
Smokers: Ciliated respiratory epithelium of the trachea and bronchi 🡪 squamous epithelium
Epithelium of the ducts of the salivary glands and pancreas and bile ducts in the presence of stone 🡪 squamous epithelium
Barrett's oesophagus: Squamous epithelium of the oesophagus due to prolonged exposure to stomach acid 🡪 columnar epithelium.
39
How does ageing occur?
Occurs within dividing cells: telomeres get shorter after each cell division – limiting the amount of cell division that can occur
40
Non-dividing cells:
41
What results in dermal elastosis
Accumulation of abnormal elastic in the dermis of the skin
This is the result of prolonged/ excessive sun exposure – photoaging
UV light causes protein cross-linking
42
What causes osteoporosis
Caused by loss of coupling in the bone remodelling process 🡪 increased bone resorption or deceased bone formation due to a lack of oestrogen (hence why so many women are affected after menopause)
Bone matrix is mineralised as normal, but the trabeculae are thinned – resulting in fractures from minor trauma
Liberates calcium – leading to hypercalciuria – the risk of renal stone formation
43
What happens when you age? Pathology of ageing (6)
Dermal elastosis
Osteoporosis
Cataracts
Senile dementia
Sarcopenia
Deafness
44
How do people become deaf?
Hair cells cannot divide/regenerate – hence once damaged cannot recover.
45
What causes sarcopenia?
Decreased growth hormone
Decreased testosterone
Increased catabolic cytokines.
46
What causes senile dementia?
Plaques and neurofibrillary tangles occur in the brain.
Due to brain atrophy since NERVE CELLS CAN NOT REPLICATE
47
What causes cataracts
Result of the formation of opaque proteins within the lens- results in a loss of lens elasticity
UV-B light causes protein cross-linking
48
What can osteoporosis cause?
Osteopenia
49
What cells have the greatest potential for division?
Foetal cells
50
What factors influence ageing
Genetic and environmental factors
51
Define Inflammation
the local physiological response to tissue injury
52
What are the 3 aims of inflammation?
1. To bring defence cells (immune cells) to the area.
2. Inactivate and/or destroy invaders
3. Begin the repair
53
How is inflammation clinically denoted as
by the suffix -itis
54
Benefits of inflammation
Destruction of invading microorganisms
The walling off of an abscess cavity, thus preventing the spread of infection
55
Problems with inflammation
An abscess in the brain would act as a space-occupying lesion compressing vital surrounding structures.
Fibrosis resulting from chronic inflammation may distort the tissues and permanently alter their function.
56
What are the signs of acute inflammation
Heat
Pain
Redness
Swelling
These four signs combine to cause the fifth sign, which is the temporary loss of function.
These signs are produced by rapid vascular response
57
2 different types of leukocytes
Granulocyte
Agranulocyte
58
What cells are classified as granulocytes
Neutrophils
Eosinophils
Basophils
Mast cells
59
What cells are classified as agranulocytes
Lymphocytes
Monocytes
60
What can monocytes differentiate into?
Macrophage
Dendritic cells
61
Cells involved in inflammation
Neutrophil polymorphs
Macrophages
Lymphocytes
Endothelial cells
Fibroblasts
62
What are neutrophil polymorphs
First on the scene of acute inflammation
Cytoplasmic granules full of enzymes that kill bacteria
Usually die at the scene of inflammation.
Release chemicals that attract other inflammatory cells, such as macrophages
63
What properties do macrophages possess
Phagocytic properties
64
Are macrophages long-lived or short-lived cells
Long-lived cells (weeks to months)
65
What are macrophages involved in
Involved in inflammation
66
How are macrophages named?
Named according to the location:
Kupffer cell (liver)
Melanophage (skin)
Osteoclast (bone)
Microglial cell (brain)
Alveolar/ peritoneal macrophages
67
Describe macrophages
Ingest bacteria and debris
May carry debris away.
May present antigens to lymphocytes.
68
Are lymphocytes long-lived or short-lived
Long-lived cells (years)
69
What are lymphocytes involved in
Involved in inflammation
70
Describe lymphocytes
Produce chemicals which attract other inflammatory cells
Immunological memory for past infections and antigens
71
What are endothelial cells
Line capillary blood vessels in areas of inflammation
72
Describe endothelial cells
Become sticky in areas of inflammation, so inflammatory cells adhere to them
Become porous to allow inflammatory cells to pass into tissues
Grow into areas of damage to form new capillary vessels
73
4 changes in local blood vessels during inflammation
1. Increased diameter
2. Increased permeability
3. Endothelial cells become 'activated.'
4. Clotting
74
Stages of inflammation
1. increased vessel permeability
2. fluid exudate
3. cellular exudate
75
Stae the 4 outcomes of inflammation
resolution
supporation
organisation
progression
76
Neutrophil action involved in inflammation
margination
adhesion
emigration
diapedesis
77
Describe fibroblasts
Long-lived cells
Form collagen in areas of chronic inflammation and repair
78
Consequences of atherosclerosis
Vessel thickening 🡪 narrowing of lumen 🡪 poor tissue perfusion
Inelasticity of vessels 🡪 predisposition to vessel rupture and haemorrhage
Alterations in vascular endothelium 🡪 increased predisposition to thrombosis
79
Name the different autopsies
Hospital autopsies: 10% of all UK autopsies
Medico-legal autopsies: 90% of all autopsies in the UK
80
How can medico-legal autopsies be further subdivided
Coronial autopsies – standard
Forensic autopsies – deaths involving crime
81
What are hospital autopsies useful for?
Useful for:
Audit
Teaching
Governance
Research
82
Types of death referred to coroners
Presumed natural
Peri/postoperative deaths
Presumed unnatural
83
What is considered a presumed natural death
Cause of death not known
Not seen by a doctor with recent illness (last 14 days)
Presumed iatrogenic
84
What is considered a presumed iatrogenic death
Anaesthetic deaths
Abortion
Complications of therapy
85
What is considered a presumed unnatural death
Accidents
Industrial death
Suicide
Unlawful killing (murder)
Neglect
Custody deaths
86
Where do referrals come from?
doctors (GMC guidance – no statutory duty to refer),
registrar of BDM (statutory duty to refer)
relatives
police
pathological technicians
other properly interested parties.
87
Coroners Act 1988
Allows coroner to order an autopsy where death is likely due to natural causes to obviate the need for an inquest.
Allows coroner to order an autopsy where death is clearly unnatural, and an inquest will be needed
88
Coroners Rules 1984
Autopsy as soon as possible
By a pathologist with suitable qualifications and experience
Report findings promptly only to the coroner
Autopsy only on appropriate premises
89
Amendment Rules 2005
The pathologist must tell the coroner precisely what materials have been retained.
The coroner authorises retention and sets a disposal date.
The coroner informs the family of the retention
The family has choices;
Return material to family
Retain for research/teaching
Respectful disposal
The coroner informs the pathologist of the family’s decision.
Pathologists to keep a record
The autopsy report must declare retention and disposal
90
Coroners and Justice Act 2009
The coroner can now defer opening the inquest and instead launch an investigation
Enshrines a system of medical examiners
Little practical change to the pathologist
Inquests now have conclusions, not verdicts
91
Human Tissue Act 2004
Autopsies are only to be performed on licensed premises
License holder
Consent from relatives for any use of tissue retained at autopsy if not subject to coronial legislation or retained for criminal justice purposes
Public display requires consent from the deceased.
Penalties include up to 3 years of imprisonment and/or a fine for not following the human tissue act.
92
laws related to autopsies
The Coroners Act 1988
Coroners Rules 1984
Amendment Rules 2005
Coroners and Justice Act 2009
Human Tissue Act 2004
93
What is the coronial autopsy
A systematic scientific examination that helps the coroner determine who the deceased was, when and where they died and how they came about their death
94
Most deaths will prove to be from
natural causes
95
By what are autopsies regulated by
legislation
96
How are autopsies performed
on the instruction of a Medico-legal authority
97
Causes of acute inflammation (5)
1. Physical events e.g trauma, heat, cold, UV light, radiation
2. Irritant and corrosive chemical substances e.g. acids and alkalis
3.Microbial infections
4.Immune-mediated hypersensitivity reactions e.g hay fever
5.Tissue necrosis e,g ischaemia resulting in myocardial infarction
98
Causes of chronic inflammation (4)
Develops as a primary response to 🡪
microorganisms resistant to phagocytosis or intra-cellular mechanisms e.g TB
Endogenous/exogenous foreign bodies
Some autoimmune disease
Primary granulomatous disease
99
When does inflammation become chronic?
Over a long period of time with simultaneous tissue destruction and attempted repair
May occur secondary to acute inflammation due to the persistence of the causative agent
100
Comparison of acute and chronic inflammation
101
Sequence of inflammation
102
What is the characteristic cell recruiting cells in acute inflammation
Neutrophil polymorph
103
Define resolution (acute inflammation)
complete restoration of the tissues to normal after an episode of acute inflammation
104
Define suppuration
formation of pus: a mixture of living, dying and dead neutrophils and bacteria, cellular debris and globules of lipid
105
Define organisation
tissue replacement by granulation tissue as part of the process of repair.
106
What does acute inflammation response involve
1. Changes in vessel calibre and flow
2. Increased vascular permeability and formation of the fluid exudate
3. Formation of the cellular exudate – emigration of the neutrophil polymorphs into the extravascular space
107
Example of acute inflammation
acute appendicitis 🡪
Unknown precipitating factor
Neutrophils appear
Blood vessels dilate
Inflammation of the serosal surface occurs
Pain felt
The appendix is either surgically removed or inflammation resolves, or the appendix bursts with generalised peritonitis and possible death
108
Example of chronic inflammation
tuberculosis 🡪
No initial acute inflammation
Mycobacteria ingested by macrophages
Macrophages often fail to kill the mycobacteria
Lymphocytes appear
Macrophages appear
Fibrosis occurs
109
Define granulomas
a collection of epithelioid histiocytes (macrophages)
110
What do granulomas all secrete, and what do they act as?
ACE act as a blood marker
111
Define Granulation tissue
an important component of healing and comprises small blood vessels in a connective tissue matrix with myofibroblasts
112
What can be used to treat inflammation, and how does it work?
Ibuprofen inhibits prostaglandins synthase
Prostaglandins = chemical mediators of inflammation.
113
Define resolution (healing and repair)
Initiating factor removed
Tissue undamaged or able to regenerate
114
An organ that can repair and heal (lung-related)
Lobar pneumonia 🡪
It affects a lobe of the lung rather than the whole thing (bronchopneumonia)
Alveoli filled with neutrophil polymorphs (acute inflammation) rather than air
Pneumocytes that line the alveoli can regenerate so the lung can be regenerated – the pneumocytes divide and reline the alveoli.
115
Summary of skin wound: abrasions
Normal skin 🡪 abrasion 🡪 scab formed over surface 🡪 epidermis growing out from adnexa, produced by scab 🡪 thin confluent epidermis 🡪 final epidermal regrowth
116
Example of how skin may heal by the first intention
Cut
117
Example of how skin may heal by second intention
Ulcer
118
Summary of Incised skin wounds: healing by 1st intention
1st intention – can suture up the cut
Incision 🡪 exudation of fibrinogen 🡪 weak fibrin join 🡪 epidermal regrowth, and collagen synthesis 🡪 strong collagen join
119
Summary of tissue loss: healing by 2nd intention
A tissue loss injury or another reason that the wound margins are not apposed requires another mechanism for repair.
You can’t bring the skin edges together. The cut is too deep.
Loss of tissue 🡪 granulation tissue 🡪 organisation 🡪 early fibrous scar 🡪 scar contraction.
Phagocytosis to remove any debris
Granulation tissue to fill in defects and repair specialised tissues lost.
Epithelial regeneration to cover the surface
120
Describe repair (healing and repair)
4 components
Initiating factor still present
Tissue damaged and unable to regenerate
Replacement of damaged tissue by fibrous tissue
Collagen produced by fibroblasts
121
Examples of wound repair
Heart after myocardial infarction
Brain after cerebral infarction (fibrosis in the brain -> gliosis)
Spinal cord after trauma
122
Cells that regenerate
Hepatocytes
Pneumocytes
All blood cells
Gut epithelium
Skin epithelium
Osteocytes – help remodel bone fractures
123
Cells that don’t regenerate
Myocardial cells
Neurones
124
Define organisation (healing and repair)
The organisation is the process whereby specialised tissues are repaired by forming mature fibrovascular connective tissue.
It occurs through the production of granulation tissue and the removal of dead tissue by phagocytosis.
125
What is granulation tissue
repair phenomenon
Loops of capillaries supported by myofibroblasts which actively contract to reduce wound size; this may result in a structure later.
126
Why are blood clots rare
Laminar flow – cells travel in the centre of arterial vessels and don’t touch the sides
Endothelial cells that line vessels are not ‘sticky’ when healthy
127
What prevents us from bleeding to death
Clot-forming cells and proteins are present in the blood to stop us bleeding to death if we cut or scratch ourselves
128
Define thrombus
solid mass of blood constituents formed within an intact vascular system during life
129
What is the Virchows triad
Factors that predispose any blood vessel to thrombosis:
Change in the vessel wall
Change in blood flow
Change in blood constituents
130
What drug reduces the risk of thrombosis
Low-dose aspirin inhibits platelet aggregation.
131
Define embolism
the process of a solid mass in the blood being carried through the circulation to a place where it gets stuck and blocks the vessel
132
Define embolus
mass of material in the vascular system able to become lodged within a vessel and block it
133
Causes of embolus
Usually caused by a part of a thrombus that has broken off and circulates in the blood stream (only small vessels can become blocked).
Less common causes are:
Air (pressurised systems of intravenous fluids/ bloods)
Tumour
Amniotic fluid (rare in pregnant women)
Fat (severe trauma with fractures)
134
Example of thrombus
When a thrombus forms in an artery, such as in the heart or brain, it is called an arterial thrombosis
135
What happens when embolus enters venous system
will travel to the vena cava and lodge in the pulmonary arteries. The lungs then act as a filter for venous emboli, because the blood vessels split down to capillary size, which is too small for the embolus to travel through
136
What happens when embolus enters arterial system
can travel anywhere downstream of its entry point
137
Reduction in blood flow can result in
Ischaemia
Infarction
End artery supply
138
Define ischaemia
reduction of blood flow to a tissue without any other implications
139
Define infarction
reduction of blood flow to a tissue that is so reduced that it cannot even support mere maintenance of the cells in that tissue so they die
140
Define end artery supply
An organ that only receives blood supply from one artery
141
Why are end arterial supplies problematic when a thrombus forms
because the whole blood supply to that organ is cut off leading to infarction
142
What organs survive if a thrombus occurs in one arterial supply and why?
multiple arterial supplies
Pulmonary arteries and bronchial arteries supplying the lungs
Portal vein and hepatic artery supplying the liver
Some parts of the brain – the circle of Willis
143
What is atheroma
Degeneration of the walls of the arteries is caused by accumulated fatty deposits and scar tissue, leading to circulation restriction and risk of thrombosis.
The fatty material forms deposits in the arteries.
144
Apoptosis in disease
cancer: lack of apoptosis – mutated p53 gene producing faulty p53 protein
HIV: too much apoptosis – kills the antibodies in the blood so the body can’t defend itself.
145
Apoptosis can be triggered by
DNA damage
Single-strand break
Base alteration
Cross-linkage
146
Mechanism of apoptosis
Initiation: Intrinsic/Extrinsic/Cytotoxic
Execution
Phagocytosis
147
Define Carcinogenesis
the transformation of normal cells to neoplastic cells through permanent genetic alterations or mutations
148
What does carcinogenesis apply to
malignant neoplasms
149
Oncogenesis refers to
same process only it applies to malignant or benign tumours
150
Is carcinogenesis a multi-step process
Yes
151
Define Carcinogens
Agents known or suspected to cause tumours
* Act on DNA i.e. are mutagenic
152
Carcinogenic vs Oncogenic
Carcinogenic = cancer causing
Oncogenic = tumour causing
153
Problems with identification of carcinogens
The latent interval may last decades
Complexity of environment
Ethical constraints
154
Epidemiological evidence of carcinogensis
Hepatocellular carcinoma
-Uncommon in UK/USA
-Common in areas with ↑ Hepatitis B/C and mycotoxins
Oesophageal carcinoma
-↑↑ incidence in Japan, China, Turkey and Iran
-? Dietary factors (Linhsien chickens)
155
Occupational/ behavioural risks of carcinogensis
* Lung cancer – strong association with smoking
* Bladder cancer – increased incidence in aniline dye and rubber industries
* Scrotal cancer – increased incidence in chimney sweeps
156
Direct evidence of carcinogenesis
Thorotrast
Thyroid irradiation
157
Experimental evidence of carcinogenesis
Incidence of tumours in laboratory animals
Cell/tissue cultures
Mutagenicity testing in bacterial cultures
158
Issues with experimental evidence of carcinogenesis
Animals/cultures may metabolise agents differently from humans
The bacterial mutation may not = carcinogenicity
159
Classes of carcinogens
Chemical
Viral
Ionising and non-ionising radiation
Hormones, parasites and mycotoxins
Miscellaneous
160
Describe Chemical carcinogens
o No common structural features
o Some act directly
o Most require metabolic conversation from pro-carcinogens to ultimate carcinogens
o Enzyme required may be ubiquitous or confined to certain organs
161
Chemical carcinogens and corresponding tumours
162
Radiant energy carcinogens
Exposure to UVA or UVB
Ionising radiation
Long term effect
163
Where would you find radiant energy carcinogens and related cancer
Skin cancer in radiographers
Lung cancer in uranium miners
Thyroid cancer in Ukrainian children
164
Biological agents carcinogens
Hormones
Mycotoxins
Parasites
165
Miscellaneous carcinogens include
Asbestos
Metals
166
Host factors for developing cancer
Ethnicity:
Decreased skin cancer in black people (melanin)
Increased oral cancer in India, SE Asia (reverse smoking)
Diet / Lifestyle
Constitutional factors - age, gender etc:
Inherited disposition
Age – incidence increases with age
Gender – breast cancer F:M = 200 (more common in women)
Premalignant lesions:
Identifiable local abnormality associated with increased risk of malignancy at that site, e.g. colonic polyps, undescended testis, cervical dysplasia
Transplacental exposure
167
Overview of how healthy cells are placed with cancerous cells
A single cell acquires mutations to become cancerous, and then this divides and divides until all of the healthy cells have been replaced with cancerous cells
168
In-situ neoplasia
* Only applies to epithelial neoplasms
* May progress to invasive disease
* Basement membrane is intact
* Screening may allow detection and treatment before the development of carcinoma
169
Describe carcinoma in-situ
a malignant epithelial neoplasm that has not yet invaded through the original basement membrane
170
Describe what is meant by invasive carcinoma
a carcinoma that has breached the basement membrane – it can now spread elsewhere
171
What is micro-invasive carcinoma
has breached the basement membrane but hasn’t invaded very far away from the original carcinoma
172
What is the defining feature of malignant neoplasm
Invasion
173
What does invasion enable neoplastic cells to do?
Enables the neoplastic cells to spread directly through tissue and gain access to blood vessels and lymphatic channels
174
What is invasion dependent upon
decreased cellular adhesion
abnormal cellular motility
production of enzymes with a lytic effect on the surrounding tissues
175
What is metastasis
Process by which a malignant tumour spreads from its primary site to produce secondary tumours at distant sites
176
Name the ways that metastasis may occur.
via :
blood vessels
lymphatics
across body cavities
along nerves
result of the direct implantation of neoplastic cells during a surgical procedure
177
What is included in the metastatic cascade
Detachment
Invasion
Intravasation
Evasion of host defences
Arrest
Extravasation
Vascularisation
178
How do neoplastic cells invade
through the basement membrane
179
Describe intravasation in the metastatic cascade
Collagenases
Cell motility
180
Describe evasion of host defence in the metastatic cascade
Aggregation with platelets
Shedding of surface antigens
Adhesion to other tumour cells
181
Describe extravasation in the metastatic cascade
Adhesion receptors
Collagenases
Cell motility
182
Describe vascularisation in the metastatic cascade
Growth at the metastatic site using autocrine growth factors. Once the tumour reaches 1mm in diameter, they begin to grow its own blood vessels (angiogenesis).
183
Angiogenesis promoters
o Vascular endothelial growth factors
o Basic fibroblast growth factor
184
Angiogenesis inhibitors
o Angiostatin, endostatin, vasculostatin
185
Routes of metastasis
It can invade the arterial side if it grows large enough and breaks off
* Haematogenous
* Lymphatic
* Trans-coelomic
186
Haematogenous route of metastasis
by the bloodstream
Forms secondary tumours in organs perfused by the blood that has drained from a tumour
187
Lymphatic route of metastasis
lymph channels
form secondary tumours in the regional lymph nodes
188
Trans-coelomic route of metastasis
pericardial and peritoneal cavities where this invariably results in a neoplastic effusion
189
Tumours which more commonly metastasise to the lung are
sarcomas and any common cancers
190
Tumours which more commonly metastasise to the liver are
colon, stomach, pancreas, and carcinoid tumours of intestine
191
Tumours that more commonly metastasise to bone are
prostate, breast, thyroid, lung and kidney
192
What is a dominant single-gene disorder?
Dominant single-gene disorders will produce the disease where there is only one copy of the abnormal gene.
193
What is a recessive single-gene disorder?
Recessive single-gene disorders will only be expressed if both gene copies are abnormal.
194
Define acquired disease
Disease caused by non-genetic environmental factors
195
What are neutrophil polymorphs involved in?
Involved in inflammation
196
Are neutrophil polymorphs short-lived or long-lived?
Short lived
197
Define neoplasm
Lesion resulting from the autonomous or relatively autonomous abnormal growth of cells which persists after the initiating stimulus has been removed – a new growth.
198
Define tumour
any abnormal swelling, e.g. neoplasm, inflammation, hypertrophy, hyperplasia
All neoplasms are tumours, but not all tumours are neoplasms
199
Are neoplasms:
Normal/abnormal
Harmful/Unharmful
Abnormal
Can be harmful or unharmful
200
What is neoplasia
autonomous, abnormal, persistent new growth
201
Tumour classification based on behaviour
Benign
Borderline
Malignant
Borderline tumours (e.g. some ovarian lesions) defy precise classification
202
What do solid neoplasms always have?
What is the one exception to this
Exception is leukaemia
203
What are neoplastic cells derived from?
Nucleated cells
204
What is essential for neoplasm growth
Angiogenesis essential for growth
205
Methods of classification of neoplasms
Behavioural: benign/malignant
Histogenetic: cell of origin
206
Benign neoplasms
Localised, non-invasive
Close resemblance to normal tissue
Circumscribed or encapsulated
Nuclear morphometry is often normal
Necrosis/Ulceration rare
Growth on mucosal surfaces is often exophytic
207
Do benign neoplasms fast or slow growth rate
Slow growth rate?
208
Mitotic activity of benign neoplasms
Low-mitotic activity
209
Why worry about "benign" neoplasms
They cause morbidity and mortality:
Pressure on adjacent structures
Obstruct flow
Production of hormones
Transformation to malignant neoplasm
Anxiety
210
Malignant neoplasms growth rate?
Rapid growth rate
211
Malignant Neoplasms
Invasive
Metastases
Variable resemblance to normal tissue
Poorly defined or irregular border
Hyperchromatic nuclei
Pleomorphic nuclei
Necrosis/Ulceration common
Growth on mucosal surfaces and skin is often endophytic
Encroach upon and destroy surrounding tissue
Are poorly circumscribed
212
Describe mitotic activity in malignant neoplasms
Increased mitotic activity
213
Describe the surface of malignant neoplasms
Have a ‘crab-like’ cut surface (Latin: cancer)
214
Why worry about “malignant” neoplasms?
They cause morbidity and mortality:
Destruction of adjacent tissue
Metastases
Blood loss from ulcers
Obstruction of flow
Hormone production
Paraneoplastic effects
Anxiety and pain
215
Histogenetic Classification
Histogenesis: the specific cell of origin of a tumour
Histopathological examination
Specifies tumour type
216
Nomenclature of Neoplasia: Neoplasms may arise from
Epithelial cells
Connective tissues
Lymphoid/haematopoietic organs
217
Suffix of neoplasms
-oma
218
Prefix of neoplasms
Prefix depending on behavioural classification and cell type
219
Define carcinoma
Malignant epithelial neoplasm
220
Benign epithelial neoplasms: papilloma
Benign tumour of non-glandular, non-secretory epithelium
Prefix with a cell type of origin e.g. squamous cell papilloma
221
Benign epithelial neoplasms: adenoma
Adenoma - benign tumour of the glandular or secretory epithelium
Prefix with cell type of origin e.g. colonic adenoma, thyroid adenoma.
222
Malignant epithelial neoplasms: Carcinoma
malignant tumour of epithelial cells
Prefixed by name of epithelial cell type e.g. urothelial Ca.
Carcinomas of glandular epithelium = Adenocarcinomas
223
Benign connective tissue neoplasms
Named according to cell of origin, suffixed by ‘-oma’
Lipoma: adipocytes
Chondroma: cartilage
Osteoma: bone
Angioma: vascular
Rhabdomyoma: striated muscle
Leiomyoma: smooth muscle
Neuroma: nerves
224
Liposarcoma =
Sarcoma of adipose tissue
225
Rhabdomyosarcoma =
Sarcoma of striated muscle
226
How are Carcinomas and Sarcomas further classified
according to degree of differentiation
227
Where the cell type of origin is unknown, the tumour is said to be
anaplastic
228
Which "omas" are not neoplasms
granuloma, mycetoma, tuberculoma
229
Not all malignant tumours are carcinoma or sarcoma e.g
melanoma: malignant neoplasm of melanocytes
Mesothelioma: malignant neoplasm of mesothelial cells
lymphoma: malignant neoplasm of lymphoid cells
