Pathology Flashcards
(153 cards)
1
Q
What is inflammation?
A
The local physiological response to tissue injury. No the disease itself, but a manifestation of disease.
2
Q
What is a benefit of inflammation?
A
The destruction of invading microorganisms and the walling off an abscess cavity, preventing spread of infection
3
Q
What is acute inflammation?
A
The initial and often transient series of tissue reactions to injury.
4
Q
What is chronic inflammation?
A
The subsequent and often prolonged tissue reactions following initial response.
5
Q
What are the steps of acute inflammation?
A
1) Initial reaction of tissue to injury
2) Vascular - dilation of vessels & increased blood flow
3) Exudative - vascular leakage of protein-rich fluid and neutrophil attracted to site of injury by chemotaxins
4) Neutrophil polymorph - migrate to plasmatic zone(area near wall of blood vessel)
- adhesion to endothelium
- emigration, neutrophils pass through endothelial cells onto basal lamina
- Diapedesis (passage of RBCs through intact walls of capillaries) RBCs may also escape
6
Q
Outcomes of acute inflammation?
A
1) resolution - restoration of tissue
2) suppuration - formation of pus leading to abscess and scaring
3) organisation - replacement by granulation tissue (new connective tissue), new capillaries grow into inflammatory exudate, macrophages migrate, fibrosis occurs
4) progression - causative agent not removed so moves to chronic inflammation
7
Q
What are the causes of acute inflammation?
A
1) microbial infections (pyogenic bacteria, viruses)
2) Hypersensitivity (parasites, tubercle bacilli)
3) Physical agents (trauma, ionising radiation, heat, cold)
4) Chemical (corrosives, acid)
5) bacterial toxins
6) tissue necrosis (ischaemic infarction - block in blood vessels)
8
Q
Appearances of acute inflammation (5 Cardinal signs):
A
1) Rubor (redness) - due to dilation of small blood vessels within the damaged area
2) Calor (heat) - due to increased blood flow (hyperaemia), resulting in vascular dilation and delivery of warm blood to the area (systemic fever from chemical mediators)
3) Tumor (swelling) - oedema, accumulation of fluid in extravascular space and inflammatory cells migrating to area
4) Dolor (pain) - from stretching and distortion of tissues due to inflammatory oedema and pus. Prostaglandins and serotonin induce pain.
5) loss of function - inhibited by pain, or severe swelling immobilises tissue
9
Q
In acute inflammation, what causes increased vascular permeability?
A
- immediate transient chemical mediators e.g. histamine, bradykinin, nitric oxide, platelet activating factor, C5a, leucotriene B4
- immediate sustained severe direct vascular injury
- delayed prolonged endothelial cell injury e.g. x-rays, bacterial toxins
10
Q
In acute inflammation, how is the cellular exudate formed?
A
- Accumulation of neutrophil polymorphs within the extracellular space (histological feature)
1) neutrophils move to sides of vessels (margination)
2) line the walls (pavementing)
2) Pass between endothelial cells
3) pass through basal lamina and migrate into adventitia
11
Q
What chemical mediators are involved in acute inflammation?
A
Histamine & thrombin
- released by original inflammatory stimulus cause up-regulation of adhesion molecules on the surface of endothelial cells (increased neutrophil adhesion)
12
Q
What do these endogenous chemical mediators in acute inflammation cause?
A
- vasodilation
- emigration of neutrophils
- chemotaxis (movement of organism towards a chemical stimulus)
- increased vascular permeability
- itching and pain
13
Q
What are the 4 enzymatic cascade systems contained in plasma?
A
1) complement
2) the kinins
3) coagulation factors
4) fibrinolytic system
14
Q
What endogenous chemical mediators cause vascular dilation?
A
Histamine (cause relaxation of muscle through increased Ca2+)
Prostaglandins
PGE2/I2
VIP
Nitric oxide
PAF
15
Q
What endogenous chemical mediators cause increased vascular permeability?
A
Transient phase - histamine
Prolonged phase - bradykinin, nitric oxide
16
Q
What chemical mediators cause adhesion of leucocytes?
A
Up-regulation of adhesion molecules on endothelium by IL-8, C5a, Leucotriene B4, PAF
17
Q
What chemical mediators are involved in neutrophil polymorph chemotaxis?
A
Leucotriene B4
IL-8
18
Q
What is the role of neutrophil polymorph in acute inflammation?
A
1) ingest bacterium
2) bacterium lies within a phagocytic vacuole (phagosome)
3) lysosomes fuse with phagosome and enzymes digest bacteria (phagolysosomes)
4) Bacterial debris released from neutrophil polymorph and lysosomes replenished
19
Q
What are the special macroscopic appearances of acute inflammation?
A
1) serous
2) suppurative inflammation - producing pus
3) membranous inflammation
4) pseudomembranous inflammation
5) necrotising (gangrenous) inflammation - tissues start to die
20
Q
What are the systemic effects of inflammation?
A
- Pyrexia (increased body temp)
- constitutional symptoms
- weight loss
- reactive hyperplasia (enlargement) of the reticuloendothelial system (monocytes and descendants)
- haematological changes
- amyloidosis (build up of protein amyloid stopping organs from working properly)
21
Q
What is cellulitis?
A
The skin over the lateral part of the foot is red (erythema) due to vascular dilatation due to acute inflammation
22
Q
What is early acute appendicitis?
A
Appendix is swollen due to oedema, the surface is covered by fibrinous exudate and the blood vessels are prominent due to dilation
(good example of acute inflammation)
23
Q
What is a granuloma?
A
A small area of chronic inflammation characterised by collection of macrophages (& T helper cells).
24
Q
How are granulomas formed?
A
In response to chronic inflammation
1) antigen from causative pathogen is taken up by macrophage
2) then presented to CD4+ helper T cells
3)CD4+ helper T cells convert to TH1 subtype
4) TH1 cells secrete IL-2 & INy
5) T cells proliferation and macrophage activation
6) macrophages & T-cells secrete TNF alpha
7) Increased accumulation of inflammatory cells
25
What are the types of granulomas?
Caseating
- central region of necrosis
- usually in lungs
- form in response to infection
- appear 'cheese-like'
Non-caseating
- No central region of necrosis
- occurs more commonly
- response to contact with foreign material, sarcoidosis (small patches of swollen tissue to develop in body's organs) and Crohn's disease
26
What are the causes of chronic inflammation?
- resistance of infective agent (TB)
- endogenous material (necrotic tissue)
- exogenous material ( asbestos, silica)
- autoimmune conditions
- primary granulomatous diseases
- transplant rejection
- continued acute inflammation
27
What cells are involved in chronic vs acute inflammation?
Acute
- neutrophils, monocytes
Chronic
- B lymphocytes -> plasma cells -> antibodies
- macrophages -> cytokines
- t lymphocytes -> cell mediated immunity
- granulomas -> aggregate of epithelia histiocytes
28
What is the macroscopic and microscopic appearance of chronic inflammation?
Macroscopic appearance:
Chronic ulcer
Chronic abscess cavity
Granulomatous inflammation
Fibrosis
Microscopic appearance:
Characteristically lymphocytes, plasma cells and macrophages
Exudation is not a common feature
Evidence of continuing destruction
Possible tissue necrosis
29
Who performs which autopsies?
Histopathologists
- hospital autopsies
- coronial autopsies (natural deaths, drowning, suicide, accidents, car accidents)
Forensic pathologists
- coronial autopsies (homicide, death in custody, neglect)
30
What are fibroblasts?
Produce collagenous connective tissue in scarring following some types of inflammation
(produce collagen)
31
What are macrophages?
- WBCs
- live longer than neutrophils
- phagocytose debris and bacteria
- transport material to lymph nodes
- may present antigen to lymphocytes
e.g., kupffer in liver, osteoclast, microglial
32
What are lymphocytes?
- long lived cells
- very small cytoplasm as don't produce proteins
- plasma cells produce antibodies
33
What are neutrophil polymorphs?
- short lived cells
- first on the scene of acute inflammation
- cytoplasmic granules full of enzymes that kill bacteria
- die at site of inflammation and then phagocytose
34
What is the sequence of chronic inflammation?
1) no or very few neutrophils
2) macrophages and lymphocytes, then usually fibroblasts
3) can resolve if no tissue damage but ends up with repair and scarring
35
Is Tuberculosis acute or chronic inflammation?
Chronic inflammation
but no initial acute inflammation (no neutrophils)
- just has macrophages
36
How to treat inflammation?
- ice (stops blood vessels dilating and fluid being exudated)
- Anti-histamine -> block histamine reducing inflammation
- ibuprofen -> inhibit prostaglandin synthetase
- steroid cream (prevent the persons system from reacting to the bacteria)
37
What is resolution and repair?
Resolution
- initiating factor removed
- tissue undamaged or able to regenerate
Repair
- initiating factor still present
- tissue damaged and unable to regenerate
38
What does repair involve? And examples of when organs cannot resolve?
- replacement of damaged tissue by fibrous tissue (when it can't regenerate)
- collagen produced by fibroblasts
Examples:
- heart after myocardial infarction
- brain after cerebral infarction
- spinal cord after trauma
39
What is healing by 1st intention?
when the wound edges are approximated e.g., sutures, stitches
(leaves only a thin scar)
incision -> exudation of fibrinogen -> weak fibrin joint -> epidermal regrowth and collagen synthesis -> strong collagen join
40
What is 2nd intention healing?
A tissue loss injury or another reason that the wound margins are not apposed
- can't bring edges together
- granulation tissue to fill in defects and repair specialised tissues lost
- loss of tissue -> granulation tissue -> organisation -> early fibrous scar -> scar contraction
41
Which cells regenerate?
- Hepatocytes
- pneumocytes
- all blood cells
- gut epithelium
- skin epithelium
- osteocytes
42
Which cells don't regenerate ?
myocardial cells
neurones
43
Why don't blood clots form all the time?
1) Laminar flow - cells travel in the centre of arterial vessels and don't touch the sides
2) Endothelial cells - that line vessels are not 'sticky' when healthy
44
What is a thrombosis?
The formation of a solid mass from blood constituents in an intact vessel in a living person.
45
What is thrombosis caused by?
Virchow's triad:
1) change in vessel wall
2) change in blood flow
3) change in blood constituents
46
What is the process of the formation of an arterial thrombosis?
1) Atheromatous plaque may have a fatty streak
2) Plaque grows and protrudes into the lumen causing turbulence in blood flow
3) Turbulence results in loss of intimal cells
4) Fibrin deposition and platelet clumping occurs
5) Keeps going to form first layer of thrombus
6) This layer allows for the precipitation of a fibrin mesh -> traps RBCs
7) Protrudes further causing more turbulence and more platelet deposition
8) Thrombi grow in direction of blood flow (propagation)
47
What are the differences between venous and arterial thrombosis?
Venous thrombosis:
- thrombi begin at valves
- commonly caused by stasis
- when blood pressure falls, flow through veins slow, allowing for a thrombus to form
- low pressure
- mainly made of RBCs
- Anti-coagulants (warfarin)
Arterial Thrombosis:
- commonly caused by atheroma
- high pressure
- mainly made of platelets
- can lead to MI/stroke
- anti-platelets
48
What are the fate of thrombi?
1) Resolve - body dissolves and clears it
2) Organised - becomes a scar, results in slight narrowing of the vessel lumen
3) Recanalisation - intimal cells may proliferate, capillaries grow into thrombus and fuse to form larger vessels
4) Embolus - fragments of the thrombus break off into the circulation
49
What is an embolism?
Mass of material in vascular system that lodges in a vessel and blocks lumen
50
What are the causes of an embolism?
- most commonly a thrombus (e.g. deep vein thrombosis)
- air (from intravenous fluids)
- cholesterol crystals (atheromatous plaque)
- tumour
- amniotic fluid
- fat (severe trauma with multiple fractures)
51
Types of emboli:
1) Venous embolism - will travel to the vena cava and lodge in pulmonary arteries
(cannot enter arteries because blood vessels in lungs split down to capillaries)
2) Arterial embolism - can travel anywhere downstream of its entry point
52
What is ischaemia?
A reduction of blood flow to a tissue or part of the body caused by constriction or blockage of blood vessels supplying it without any other implications (just reduction in blood flow)
53
What is an infarction?
It is the reduction in 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. (reduction in blood flow + death)
54
How is infarction caused?
Usually a macroscopic event caused by thrombosis of an artery, stopping blood flow to cells
55
How does aspirin help with thrombosis?
Low dose aspirin inhibits platelet aggregation, so this can be prescribed to reduce the risk of thrombosis
56
What is atherosclerosis?
Formation of atherosclerotic plaques in the intima of systemic (opposed to pulmonary) arteries.
(common in high pressure systems such as aorta and systemic arteries)
57
What are the risk factors of atherosclerosis?
Hyperlipidaemia (hypercholesterolemia) most important risk factor
Smoking
Hypertension
Diabetes
Male sex
Increasing age
58
Formation of atherosclerosis
1) Endothelial cell dysfunction (increased cholesterol)
2) High levels of LDL in the blood accumulate in arterial wall
3) Macrophages attracted to site of damage and take up LDL liquid to form foam cells
4) Formation of a fatty streak
5) Activated macrophages release products (cytokines)
6) WBCs die and more WBCs are sent, the dead cells build up to form a plaque.
7) Smooth muscle proliferation around lipid core (muscle cells form over top layer of plaque) and form a fibrous cap (collagen)
8) After growth of plaque, the fibrous cap ruptures and plaque comes into contact with the blood causing a blood clot to form.
(only in arteries)
phase1 - damage of endothelial layer
phase 2 - formation of fibrous cap
59
How is a venous thrombus formed?
Mainly around valves due to turbulent blood flow
1) damage to endothelial cells in the vessel causes cells to lift from vessel wall, exposing collagen
2) platelets then begin to stick to this exposed collagen and release chemicals which cause platelet aggregation and starts off cascade of clotting proteins
3) RBCs then get trapped within the aggregating platelets
4) clotting factors join the red blood cells and platelets, and the clotting cascade forms a large protein molecule fibrin, which then gets deposited and forms the clot
5) positive feedback loop -> can end up causing a thrombus, blocking the artery
60
What is end artery supply?
AN organ that only receives blood supply from one artery so if thrombus forms the whole blood supply to an organ is in infarct.
Except some organs have multiple arterial supplies:
- liver -> portal vein and hepatic artery
- lungs -> pulmonary arteries and bronchial arteries
- brain -> circle of willis
61
What is an atheroma?
- The fatty material which forms deposits in the arteries.
- Degeneration of the walls of the arteries caused by accumulated fatty deposits and scar tissue, and leading to restriction of the circulation and risk of thrombosis.
62
What is the time course and first signs for atherosclerosis?
- does not increase significantly until 50's
- first signs of atherosclerosis are fatty streaks which aren't plaque just lipids under intimal of aorta
63
What are the constituents of plaque?
- Fibrous tissue
- lipids -> cholesterol
- lymphocytes -> chronic inflammation
64
What is apoptosis?
Programmed cell death
- non-inflammatory
- sometimes pathological if out of control
- mitochondrial factor release (cause cell death)
- cell membrane intact
- p53 is a protein in cells which can detect DNA damage and trigger apoptosis
65
What is necrosis?
Traumatic cell death due to disease, injury, or failure fo blood supply that indices inflammation and repair
- not planned
- inflammatory
- always pathological
- macrophage digestion
- cell membrane destroyed
66
Clinical examples of necrosis?
- toxic spider venom
- frostbite
- cerebral infarction
- avascular necrosis of bone -> femur has single arterial supply through the neck of the femoral head
- pancreatitis (due to containing lots of enzymes, starts eating itself)
67
Examples of apoptosis in disease?
Cancer: lack of apoptosis (mutated p53 protein)
HIV: too much apoptosis, kills the antibodies in the blood so the body can't defend itself
(helper T cells - CD4)
68
What are the inhibitors and inducers of apoptosis?
Inhibitors
- growth factors
- extracellular cell matrix
- sex steroids
Inducers
- Glucocorticoids
- free radicals
- ionising radiation
- DNA damage
(BAX & BAK)
69
What is the intrinsic pathway of apoptosis?
An injury occurs within the cell and the resulting stress activates the apoptosis pathway.
1. BAX and BAK activate the mitochondria
2. Cytochrome C is released through pores in side of mitochondria
3. Cytochrome C activates CASPASES
4. CASPASES kills the cell
Bcl-2 and Bcl -xl (inhibitors) so if activated, don't cause release of cytochrome C so too many cells survive (follicular lymphoma)
Bcl-2 : BAX ratio determines the cell's susceptibility to apoptotic stimuli
BroCcoLi keeps you alive
70
What is the extrinsic pathway of apoptosis?
It begins outside a cell, when conditions in the extracellular environment determine that a cell must die.
1. Fas-Ligand can bind to Fas receptor OR TNF alpha can bind to TNF receptor
2. Activates initiator caspases
3. Activates CASPASES causing cell death
71
What is the extrinsic cytotoxic pathway of apoptosis?
1. Cytotoxic T cell binds to membrane
2. Releases Granzyme B
3. This perforates a membrane
4. And allows release of perforin, to enter cell
5. Then activates CASPASES
6. Cell death
(If you're TOXIC you'll make GRANNY PERF)
72
What are the 6 types of necrosis?
1. Coagulative - most types of ischaemia, more solid
2. Liquefactive - abscesses (Liquid-factive, occurs in brain)
3. Caseous - TB & fungi (cheese-sous)
4. Gangrene - rotting of tissue, black from iron sulphide
5. Fat - pancreatitis
6. Fibrinoid - vasculitis
73
What is a genetic disease?
A disease that occurs primarily from a genetic abnormality
74
What is an inherited disease?
Caused by an inherited genetic abnormality
- may not manifest till later in life
75
What is congenital disease?
Present at birth
- genetic or acquired
- often a disease which is due to environmental factor but may have a strong genetic background
76
What are types of inherited diseases?
o Chromosomal abnormalities - Down's syndrome
o Mendelian inheritance - dominant (sickle cell) and recessive gene diseases (single genes)
o Autosomal inheritance - on all chromosomes except sex chromosomes
o Polygenic inheritance - lost of genes acting together to cause an effect (breast cancer)
77
What is acquired disease?
Caused by non genetic environmental factors
e.g. smoking
- can be congenital (fetal alcohol syndrome)
78
What is hypertrophy?
Increase in size of a tissue caused by an increase in size of the constituent cells
(increase in cell size but NOT number of cells)
e.g., occurs in organs where cells cannot divide - skeletal muscles in athletes/bodybuilders
79
What is hyperplasia?
Increase in size of a tissue caused by an increase in number of the constituent cells
(increase in number of cells)
occurs in organs where cells can divide
e.g., benign prostatic hyperplasia, endometrial hperplasia
hyperplaSia - plural
80
What is atrophy?
Decrease in size of a tissue caused by a decrease in number of the constituent cells or a decrease in their size
e.g., Alzheimer's disease
81
What is metaplasia?
Change in differentiation of a cell from one fully differentiated type to a different fully-differentiated type
- reversible
- no premalignant potential
- adaptive response to injuries/ change in envrionment
e.g., bronchial epithelium from ciliated columnar epithelium to squamous epithelium due to smoking
82
What is dysplasia?
The imprecise term for the morphological changes seen in cells in the progression to becoming cancer
- premalignant condition characterised by increase in growth
83
What happens to telomeres as you age?
telomeres (a structure at the end of a chromosome)
get shorter after each cell division
- limits the amount of division that can occur
- eventually become so short that the chromosome cannot divide any more
e.g., skin cells slowly divide less as you age
84
What is dermal elastosis caused by?
- Accumulation of abnormal elastic in the dermis of the skin
- result of prolonged sun exposure
- UV-B light causes protein cross-linking
85
What is osteoporosis caused by?
- increase bone resorption or decreased bone formation due to lack of oestrogen
- mineralised still but trabecular are thinned making it weak
(mainly in women after menopause)
86
What are cataracts caused by?
- result of formation of opaque proteins within the lens which usually result in a lost of lens elasticity
- UV-B light causes protein cross-linking
87
What is senile dementia caused by?
Plaques and neurofibrillary tangles occur in brain
- prevented by exercise
88
What is sarcopenia caused by?
sarcopenia = loss of muscle
- decreased growth hormone
- decreased testosterone
- increased catabolic cytokines
89
What is deafness caused by?
- only born with certain number of hair cells
- hair cells in cochlear cannot divide/ regenerate so if damaged they cannot be replaced
90
What is the endothelial damaged theory?
- endothelial cells are delicate
- easily damaged by cigarette smoke, shearing forces at arterial divisions (hypertension), hyperlipdaemia, glycosylation products (from poorly controlled diabetes)
- cumulative damage leads to endothelial ulceration, mircothrombi, eventual development of established atherosclerotic plaques
91
What is the importance of apoptosis in health?
o Development - removal of cells during development
e.g. interdigital web
o cell turnover - removal of cells during normal turnover
e.g., cells in the intestinal villi at the tips, to be replaced by cells from below
92
What do granuloma's secrete?
ACE
Blood marker
93
When do you get combined hypertrophy and hyperplasia?
In pregnancy in smooth muscles cells
(increase in size and number)
occurs in organs where cells can divide
94
Which cells divide continuously and which don't?
Continuously for life = skin, gut lining cells
Stop after birth = neurone
95
How to cure cancers that stick to one area? Example?
- Complete local excision
E.g. Basal cell carcinoma of the skin - it never spreads to other parts of the body
96
How to treat white blood cells cancer? Example?
- WBCs circulate round the body and so will any tumour of WBCs
- treat with drugs which circulate the body + radiotherapy, stem cell therapy or bone marrow transplant
e.g., leukaemia
97
How do carcinomas spread around the body? (2 ways)
- Carcinomas spread to the lymph nodes that drain the site of the carcinoma
- can spread through blood to bone
e.g., breast cancer
98
What is carcinogenesis?
The transformation of normal cells to (malignant) neoplastic cells through permanent genetic alterations or mutations.
- multistep process
99
What is oncogenesis?
Benign and malignant tumours
100
What is carcinogens and oncogenes?
Agents known or suspected to cause tumours
carcinogenic = cancer causing
oncogenic = tumour causing
101
What is a neoplasm?
An autonomous abnormal growth of cells in the body which persists after the initiating stimulus has been removed.
102
What are the 5 classes of carcinogens?
Chemical
viral
Ionising and Non-ionising radiation
Hormones, parasites and mycotoxins
Miscellaneous
103
What are the characteristics of chemical carcinogens?
- Different place where they are encountered and metabolised
- no common structural features
- some act directly
- most require metabolic conversion from pro-carcinogens to ultimate carcinogens
- enzyme required may be ubiquitous or confined to certain organs
104
What are viral carcinogens? Do they cause cancer?
Viruses cause 10% of all cancers
- most oncogenic viral infections don't result in cancer
e.g., hepatitis B -> hepatocellular carcinoma, HPV -> carcinoma of cervix, penis, anus, Human herpes virus -> Kaposi
105
What are radiating carcinogens?
- exposure to UVA or UVB
- long term effect
106
What biological agents are carcinogens?
Hormones:
- increased oestrogen
- anabolic steroids
Mycotoxins
Parasites
107
What host factors cause cancer?
1) Ethnicity/race e.g., less skin cancer in darker skin
2) Diet/lifestyle e.g., exercise, unprotected sex
3) Constitutional e.g., age, gender, inherited disposition
4) Premalignant conditions e.g., identifiable local abnormalities associated with increased risk of malignancy at that site (cervical dysplasia, colonic polyps)
5) Transplacental
108
How does breast cancer arise?
- A malignant tumour arising from the epithelial cells lining the ducts and lobules of the breasts
- can drain to axillary lymphs and spread into lymph nodes
109
What is the symptoms and treatment for breast cancer?
symptoms: back pain (spreads to bone marrow) and spontaneous fractures
o A core biopsy needle used to rule out fibroadenoma
o check whether cancer has spread to axilla and do an axillary node clearance
o check whether it has metastasised to other part of body - then systematic chemotherapy needed
o if not spread can be excised during surgery
o Anti-oestrogen drugs - block oestrogen receptors on the cancer cells inhibiting their growth
110
What does Herceptin do?
A drug that binds to Her2 protein on the outside of the cell membrane
- tumours over-express a growth factor receptor on their cell surface called Her2 protein
- this drug reduces rate of growth of cancer cells
111
What is a carcinoma in situ?
A malignant epithelial neoplasm that has not yet invaded through the original basement membrane
112
What is a invasive carcinoma?
A carcinoma that has breached the basement membrane - it can now spread elsewhere
113
What is a in-situ neoplasia?
- only applies to epithelial neoplasm
- may progress to invasive
disease
- basement membrane still intact
- screening may allow detection and treatment before development of carcinoma
114
What is a micro-invasive carcinoma?
Has breached the basement membrane but hasn't invaded very far away from the original carcinoma
115
What is invasion dependent on?
- production of enzymes (proteases)
- abnormal cell motility
- decreased cellular adhesion
116
What is invasion?
When a malignant tumour breaks through the basement membrane
- enables the neoplastic cells to spread directly through tissue and gain access to blood vessels and lymphatic channels
117
What is metastasis?
Process by which a malignant tumour spreads from its primary site to produce a secondary tumour at distant sites.
118
What is the process of metastasis?
1) Detachment
2) Breach basement membrane
3) Intravasation - travel in blood or lymph nodes or across body cavities or along nerves (collagenases & cell motility)
4) Evasion of host immune defence - Not killed as they travel (aggregation with platelets, shedding of surface antigens, adhesion to other tumour cells)
5) Arrest
6) Extravasation - exit at another part of the body
7) Growth at metastatic site - divide to from more cancerous cells at another site
8) Angiogenesus - form own blood supply to form a tumour bigger than 1mm
119
What are the routes of metastasis?
1) Invade the arterial side if it grows large enough and breaks off
2) Haematogenous - by the blood stream, forms secondary tumour in organs perfused by blood that has drained from a tumour
3) Lymphatic - lymph channels, form secondary tumours in regional lymph nodes
4) Trans-coelomic - pericardial and peritoneal cavities where this invariably results in a neoplastic effusion
120
Which tumours more commonly metastasise to the lungs?
Sarcomas (connective tissue)
Any common cancers
121
Which tumours more commonly metastasise to the liver?
Colon
stomach
pancreas
carcinoid tumours of intestine
122
Which tumours more commonly metastasise to bone?
Prostate
Breast
Thyroid
Lung
Kidney
(BLT KP)
123
What makes a cell cancerous and then what does it do?
A single cell acquires mutations to become cancerous
- then divided and divides until all of the healthy cells have been replaced with cancerous cells
124
What are the benefits of targeted and conventional chemotherapy?
Conventional
- good for fast dividing tumours
- not selective for tumour cells (kills normal dividing cells as well - hair cells)
Targeted
- exploits some differences between cancer cells and normal cells to target drugs to the cancer cells (more effective, less side effects)
125
What are the promoters and inhibitors of angiogenesis?
Growth of new blood vessels
Promoters:
- vascular endothelial growth factors
- basic fibroblast
growth factor
Inhibitors
- Angiostatin, endostatin, vasculostatin
126
How does smoking increase risk for atherosclerosis?
Has free radicals, nicotine and carbon monoxide which are all damaging to endothelial cells
127
How does hypertension increase risk for atherosclerosis?
Increased pressure,
Sheering forces on endothelial cells
Increased damage of the wall
128
How does diabetes increase risk fo atherosclerosis?
- High glucose levels in the blood
- Increased free radicals --> increased oxidation of LDLs get stuck
- Loss of nitric oxide --> normally allows relaxation of vessels + increased flow
- promotes platelet aggregation
129
How does high cholesterol increase risk to atherosclerosis?
High LDLs
-> accumulates in arterial wall, causing damage
130
How does obesity increase risk to atherosclerosis?
Increases pro inflammatory cytokines
(secreted from immune cells like T cells to promote inflammation)
131
What is the difference between a neoplasm and tumour?
Tumour = any abnormal swelling e.g. neoplasm, inflammation, hypertrophy, hyperplasia
Neoplasm = whereas all neoplasm are abnormal
All neoplasms are tumours but not all tumours are neoplasms.
132
What is the structure of neoplasms?
Made up of neoplastic cells and a Stroma.
Neoplastic cells:
- from nucleated cells, monoclonal
Stroma:
- connective tissue framework
- mechanical support
- nutrition
Angiogenesis essential to growth
133
What are the methods of classification for neoplasms?
Behavioural = benign or malignant
Histogenetic = cell of origin
134
What are the behavioural classifications of neoplasm?
1. Benign
2. Borderline (defy precise classifications e.g. ovarian lesions)
3. Malignant
135
What are the characteristics of benign neoplasms?
- localised, non-invasive
- slow growth rate
- low mitotic activity
- close resemblance to normal tissue
- circumscribed or encapsulated
E.g. fibroid, Tubulovillous adenoma
136
Why worry about benign neoplasms?
Cause morbidity and mortality:
- pressure on adjacent structures
- Obstruct flow
- Production of hormones
- Transformation to malignant neoplasm
- Anxiety
137
What are the characteristics of malignant neoplasms?
- invasive
- metastases
- rapid growth rate
- variable resemblance to normal tissue
- poorly defined or irregular border
- increased mitotic activity
- necrosis common
- ulceration common
- hyperchromatic nuclei
- Pleomorphic nuclei
138
Why worry about malignant neoplasms?
Cause morbidity and mortality:
- destruction of adjacent tissue
- metastases
- blood loss from ulcers
- obstruction of flow
- hormone production
- paraneoplastic effects (difficulty walking, swallowing, talking etc.)
- anxiety and pain
139
What is histogenesis?
the specific cells of origin of a tumour
140
Which cells/tissues form which type of neoplasms?
- Epithelial cells = carcinomas
- Connective tissue = sarcomas
- Lymphoid/haematopoietic organs = lymphomas/leukaemia
neoplasm end in 'Oma'
141
What is a papilloma?
A benign tumour of non-glandular, non-secretory epithelium
(Prefix with cell type of origin e.g. squamous cell papilloma)
142
What is an adenoma?
A benign tumour of glandular or secretory epithelium
143
What is a carcinoma?
A malignant tumour of epithelial cells
(carcinoma of glandular epithelium = adenocarcinomas)
144
What are the types of benign connective tissue neoplasms?
prefix = cell of origin
suffix = 'oma'
Lipoma: adipocytes
Chondroma: cartilage
Osteoma: bone
Angioma: vascular
Rhabdomyoma: striated muscle
Leiomyoma: smooth muscle
Neuroma: nerves
145
What are types of malignant connective tissue neoplasms?
Suffix = 'sarcoma'
Liposarcoma = adipose tissue
Rhabdomyosarcoma = striated muscle
Leiomyosarcoma = smooth muscle
Chondrosarcoma = cartilage
Osteosarcoma = bone
Angiosarcoma = blood vessels
146
What '-omas' are NOT neoplasms?
- Granulomas
- mycetoma
- tuberculoma
147
Which malignant tumours are NOT named 'carcinoma' or 'sarcoma'?
o Melanoma - melanocytes
o Mesothelioma - mesothelial cells
o Lymphoma - lymphoid cells
148
What is one of the tumour types that NEVER metastasises?
Basal cell carcinoma
149
Which cancers metastasise to bone?
- breast cancer
- lung cancer
- thyroid cancer
- renal cell cancer
- prostate cancer
(BLT KP)
150
What term describes a cancer that has not invaded through the basement membrane?
Carcinoma in situ
151
Which cancer are screened for in the UK?
o Breast cancer
o Colorectal cancer
o Cervical cancer
152
What are the tumour stagings?
TMN staging:
o T - refers to the primary tumour
o N - refers to lymph node status
o M - refers to metastatic status
153
What is the role of p53 protein?
p53 protein looks for DNA damage, if damage is present p53 switches on apoptosis.
