ICS- Pathology Flashcards
(261 cards)
1
Q
Pathology- Autopsy
What is an autopsy?
A
It is the medical examination of a body after death to dermine the cause of death.
2
Q
Pathology- Autopsy
What are the different types of autopsy?
A
- Hospital autopsy (Consent autopsy)
- Medico-legal autopsy (Coronial autopsy)
3
Q
Pathology- Autopsy
Why are hospital autopsies carried out?
What percentage of autopsies are hospital autopsies?
A
For audit, teaching, governance and research
<10% of all autopsies in the uk
4
Q
Pathology- Autopsy
Why are coronial autopsies carried out?
What percentage of autopsies are medico-legal?
A
They are done upon request of the coroner to determine the cause of death.
>90% of all autopsies in the UK
5
Q
Pathology- Autopsy
Who performs autopsies?
A
Histopathologists or forensic pathologists
6
Q
Pathology- Autopsy
when do histopathologists perform autopsies?
A
when the suspected reason of death is:
* Natural
* drowning
* suicide
* accident
* fire deaths
* industrial deaths
* road traffic deaths
* peri/ post operative deaths
7
Q
Pathology- Autopsy
A
When do forensic pathologists do autopsies?
only when there is a crime involved, e.g.:
* coronial autopsy
* homicide
* death in custody
* neglect
8
Q
Pathology- Autopsy
What are the reasons for requesting an autopsy?
A
when the death is presumed natural, presumed iatrogenic or presumed unnatural
9
Q
Pathology- Autopsy
What types of death are presumed natural?
A
- when the cause of death is unknown
- When the patient had not been seen by the doctor in the last illness
10
Q
Pathology- Autopsy
What types of death are presumed iatrogenic?
A
- peri/post operative deaths
- anaesthetic deaths
- abortion
- complications of therapy
11
Q
Pathology- Autopsy
What types of death are presumed unnatural?
A
- accidents
- industrial death
- suicide
- unlawful killing
- neglect
- custody deaths
- war/ industrial pensions
12
Q
Pathology- Autopsy
Who makes referrals to the coroner for autopsies?
A
- doctors
- Registrar of births, deaths and marriages
- relatives
- police
- anatomical pathology technicians
- other properly interested parties
13
Q
Pathology- Autopsy
Who has a legal duty to refer deaths to the coroner?
A
the registrar of births, deaths and marriages
14
Q
Pathology- Autopsy
what duty do doctors have in terms of referring deaths to the coroner?
A
they have no required duty to refer, however there is a GMC duty and common law duty
15
Q
Pathology- Autopsy
what are the fundemental aspects of an autopsy (in order)
A
- History/ scene
- external examination
- evisceration
- internal examination
- reconstruction
16
Q
Pathology- Autopsy
what does an external examination involve?
A
- identification (gender, age, clothing, jewellery, etc.)
- disease and treatment
- injuries
17
Q
Pathology- Autopsy
what does evisceration involve?
A
- Y-shaped incision on chest
- open all body cavities
- examine all body organs in situ
- remove thoracic and abdominal organs
- remove brain
18
Q
Pathology- Autopsy
what does an internal examination involve?
A
- heart and great vessels
- lungs, trachea, bronchi
- liver, gall bladder, pancreas
- spleen, thymus and lymph nodes
- genitourinary tract
- endocrine organs
- central nervous system
19
Q
Pathology- Autopsy
what questions are being sought from an autopsy?
A
- who was the deceased?
- when did they die?
- where did they die?
- how did they come about their death?
20
Q
Pathology- Autopsy
what are the different types of inflammation?
A
acute and chronic
21
Q
describe the onset and duration of acute inflammation
A
this type of inflammation starts quickly, usually within minutes to hours. it’s typically short-lived, lasting a few hours to a few days, as the body attempts to address an immediate injury or infection. e.g. acute appendicitis
22
Q
describe the onset and duration of chronic inflammation
A
this has a slower onset than acute and lasts for a much longer period, ranging from weeks to months or even years. it happens when the acute response fails to fully resolve the issue, or when there is a persistent irritant or underlying condition. e.g. tuberculosis
23
Q
what is the primary purpose of acute inflammation?
A
its main goal is to address an immediate injury or infection, eliminate the initial cause of cell injury (such as an allergen) clear out dead cells and set up tissue repair. its an immediate, protective response.
24
Q
what is the primary purpose of chronic inflammation?
A
it often represents a failed resolution of acute inflammation, leading to a prolonged response that can cause tissue damag. it may result from ongoing infection, autoimmunity, or long-term exposure to harmful substances (e.g. smoking)
25
what are the cells involved in acute inflammation?
neutrophils
endothelial cells
mast cells
macrophages
platelets
26
what do neutrophils do in acute inflammation?
* mechanism of action: margination (flow close to the endothelium) adhesion (to the endothelium), emigration and diapedesis (neutrophils and other blood cells migrate through the walls of the endothelium into target tissues)
* when in target tissues they can perform phagocytosis
27
what do endothelial cells do in acute inflammation?
* vasodilation
* increased permeability to allow inflammatory cells to pass into surrounding tissue and 'becoming sticky' so that inflammatory cells adhere to them at sites of inflammation
28
what cells are involved in chronic inflammation?
Lymphocytes
macrophages
plasma cells
fibroblasts
29
what do lymphocytes do in chronic inflammation?
* they are involved in adaptive immunity, which is a hall mark of chronic inflammation, especially in autoimmune diseases.
* release chemicals which attract other cells
* T lymphocytes control your body's immune system response and directly attack and kill infected cells and tumour cells.
* B lymphocytes make antibodies.
30
what do macrophages do in chronic inflammation?
they are crucial in chronic inflammation as they play a role in both continuing the inflammatory response and in tissue repair.
31
what do plasma cells do in chronic inflammation
they produce antibodies, particularly in conditions like rheumatoid arthritis
32
what do fibroblasts do in chronic inflammation?
contribute to fibrosis (scarring) by producing collagen in chronic inflammation
33
what are the outcomes of acute inflammation?
* resolution (normal)
* supportation (pus formation)
* organisation (granulation tissue, always in cardiac tissue and neurons)
* progression (excessive recurrent inflammation, chronic)
34
what are the outcomes of chronic inflammation?
prolonged inflammation often leads to tisse danage, granulomas, fibrosis and in some cases, may contribute to diseases like atherosclerosis.
35
what is a granuloma?
a granuloma is a small, organised collection of immune cells that forms when the immune system attempts to isolate and contrain a substance it cannot eliminate, such as persistent pathogens (TB), foreign materials, or chronic irritants. Granulomas are typically seen in chronic inflammation and are a hallmark of diseases such as tuberculosis, sarcoidosis and crohn's disease.
36
what are the different parts of a granuloma?
1. core of epithelioid histiocytes
2. lymphocyte ring
3. outer fibroblast layer
37
what is the core of epithelioid histiocytes in granulomas?
at the centre are macrophages, which may differentiate into epithelioid cells (larger, specialised macrophages) or multinucleated giant cells (formed by the fusion of serveral macrophages). these cells attempt to 'wall off' the offending material.
38
what is the lymphocyte ring in granulomas?
surrounding the macrophage core is often a layer of T lymphocytes, which help sustain the inflammatory response and keep the macrophages activated
39
what are the 3 things involved in the vascular component of inflammation
1. vasodilation
2. sticky endothelium
3. increased vascular permeability
40
why is vasodilation an important vascular component of inflammation?
this happens due to inflammatory mediators such as histamins
41
why is the sticky endothelium an important vascular component of inflammation?
the endothelium becomes 'sticky' in areas of inflammation so that inflammatory cells can adhere and eventially migrate across endothelium to tissues where they are required.
42
why is increased vascular permeability an important vascular component of inflammation?
increased vascular permeability forms fluid exudate (leaked fluid in extracellular space- cause of swelling) and cellular exudate (emigration of neutrophils and other immune cells into extravascular space)
43
list the different triggers of inflammation
* infections and microbial products
* tissue damage
* foreign bodies
* immune reactions
44
how do infections and microbial products trigger inflammation?
pathogens like bacteria and viruses trigger inflammation by activating immune cells to control the infection
45
how does tissue damage trigger inflammation?
when cells are injured, they release signals that prompt immune cells to start inflammation and promote tissue repair
46
how do foreign bodies trigger inflammation?
particles such as splinters or crystals cause inflammation as the body attempts to isolate or remove the irritant
47
how do immune reactions trigger inflammation?
autoimmune responses or allergies lead to inflamation when the immune system mistakenly attacks normal tissues or reacts to harmless substances
48
list the physiological benefits of inflammation
1. defence against infections
2. tissue repair and healing
3. activation of immune responses
4. containment and resolution
49
how is defence against infections a physiological benefit of inflammation?
it mobilises immune cells (like neutrophils and macrophages to the site of infection, where they phagocytose pathogens and release antimicrobial agents to control the infection.
50
how is tissue repair and healing a physiological benefit of inflammation?
inflammation promotes the removal of dead or damage cells and stimulates the release of growth factors, facilitating tissue repair and regeneration.
51
how is activation of immune responses a physiological benefit of inflammation?
it enhances the activation and coordination of the adaptive immune system, including the activation of T and B cells, leading to a more targeted immune response.
52
how is containment and resolution a physiological benefit of inflammation?
inflammation helps isolate harmful agents (such as pathogens or irritants) to prevent their spread to healthy tissues, and once the threat is eliminated, it resolves inflammation to restore tisse homeostasis.
53
describe the pathophysiology of inappropriate inflammation
this happens in:
* autoimmune conditions such as rheumatoid arthritis
* persistent ongoing infections
* foreign body which could not be removed (granuloma formation)
* ongoing irritation or injury (e.g. chemicals inhaled from smoking)
54
what are the 5 cardinal signs of inflammation?
* redness (rubor)
* heat (calor)
* swelling (tumor)
* pain (dolor)
* loss of function
55
what are the different components of the haemostasis?
platelet plug formation
clotting cascade.
56
why are clots rare?
1. laminar flow- cells travel in the centre of arterial vessels and dont touch the sides
2. endothelial cells which line vessels are not 'sticky' when healthy.
57
define thrombosis
a solid mass of blood constituents formed within intact vascular system during life
58
define thrombus
a blood clot
59
define an embolism
a mass of material in the vascular system able to become lodged within vessels and block them
60
describe an embolus
blood clot or any other mass that travels through the blood stream
61
define ischemia
reduction in blood flow
62
describe an infarction
reduction in blood flow with subsequent death of cells
63
what is thrombosis?
the formation of a solid mass (clot), from blood components within an intact vessel. it begins with platelet aggregation, where platelets release chemicals that attact more platelets. these chemicals also initiate the clotting cascade, this leads to the formation of fibrin, a large protein that forms a mesh, this stabilises the platelet plug and traps red blood cells. the resulting strucutre is called a thrombus and usually is broken down using endogenous anticoagulants such as plasmin, but it can break off and become pathological. when this happens it is called an embolus.
64
what is an embolism?
an embolism is when a solid mass in the blood travels through the circulation and becomes lodged, blocking a vessel.
65
what are the causes of an embolism?
the most common cause is a thrombus breaking off (e.g. a deep vein thrombosis from leg veins) and travelling through the large veins and the right heart into the lungs (pulmonary embolism).
other, less common emboli incude:
* air (e.g. from IV lines, or diving)
* cholesterol crystals (from atherosclerotic plaques)
* tumour cells
66
what is a venous embolism?
travels through the vena cava, right heart, and lodges in pulmonary arteries (pulmonary embolism), as the lungs filter out emboli by narrowing to capillary size. Or if the patient has a septal defect, the thrombus can go to the left side of the heart and cause a stroke.
67
how would you treat a venous embolism?
it's mainly made of fibrin so treat with anticoagulants
68
what is an arterial embolism?
can travel anywhere downstream in the systemic circulation. for example. a thrombus in the left ventricle after a heart attack or an embolism can block arteries outside the heart and cause a stroke
69
how would you treat an arterial thrombus?
it's mainly made of platelets so treat with antiplatelets (e.g. aspirin)
70
what is ischaemia?
an ischaemia is simply a reduction of blood flow to a tissue without any other implications
71
what is an infarction?
the reduction in blood flow to a tissue that is so reduced that it cannot even support mere maintenance of cells i that tissue so they die. infarction is usually a macroscopic event caused by thrombosis of an artery, e.g. thrombus in the left anterior descending coronary artery causing infarction of the anterior wall of the left ventricle
72
what can impaired blood flow and obstruction cause?
* atherosclerosis
* thrombosis
* embolism
73
what is atherosclerosis?
the buildup of fatty plaques inside arteries leads to stenosis (narrowing) and hardening of the vessels, increasing resistance to blood flow. this reduced the amount of oxygen and nutrients reaching tissues.
74
describe vasoconstriction
in conditions such stress or cold exposure, blood vessels constrict, increasing resistance and reducing blood flow. chronic vasoconstriction can contribute to high blood pressure (hypertension)
75
describe vasodilation
conditions such as inflammation, exercise , or sepsis can cause blood vessels to dilate, loweing resistance and increasing blood flow to tissues, sometimes leading to hypotension (low blood pressure)
76
what is heart failure?
the heart's inability to pump blood effectively reduces cardiac output, leading to poor perfusion of organs and tissues. this results in symptoms like oedema (fluid retention) and fatigue due to inadequate oxygen delivery.
77
what is hypertension?
high blood pressure increases the force against the walls of arteries, causing endothelial injury and thickening of the vessel walls (atherosclerosis). over time, this leads to reduced vessel elasticity and impaired blood flow, contributing to organ damage, particularly in the heart, kidneys and brain.
78
what are the 3 components of virchow's triad?
1. endothelial injury
2. changes in blood flow
3. hypercoagulability
79
how does endothelial injury lead to pathological thrombus formation?
(e.g. from cigarette smoke) exposes procoagulant substances like tissue factor and collagen, which activate platelets and the coagulation cascade, leading to clot formation
80
how do changes in blood flow (stasis of blood) lead to pathological thrombus formation?
(like turbulence over damaged endothelium) slows down the movement of clotting factors and platelets, promoting their aggregation and increasing the likelihood of thrombus formation.
81
how does hypercoagulability lead to pathological thrombus formation?
(change in blood constituents) results in an increased tendency of the blood to clot, either by increasing the production of clotting factors or by impairing the body's natural anticoagulant mechanisms, making thrombus formation more likely.
82
why do platelet plugs not always form a thrombosis?
most thromboses are usually caused by a combination of 2 or 3 of the the components in virchow's triad.
83
what are the 6 arterial thrombi symptoms?
* pain
* pulseless
* perishingly cold
* pallor
* paraesthesia (sensation of tingling, burning, etc.)
* paralysis
84
what are the complications caused by endothelial injury?
atherosclerosis
85
what are the complications caused by stasis of blood?
varicose veins
86
what are the complications caused by hypercoagulability of blood?
cancer
87
what is resolution of tissue?
where does it usually happen?
when the initiating factor of damage is removed so initial tissue is regenerated.
it happens in liver, bone, superficial skin wounds
88
what is repair of tissue?
Where does it usually happen?
when the intiating factor of damage is still present so scar tissue is generated.
it will always happen in myocardial tissue, CNS and deep skin wounds.
89
what happens during skin abrasion? resolution or repair?
resolution
90
how does resolution of a skin abrasion take place?
1. scab forms over the surface of skin
2. epidermis grows out from adnexa, protected by the scab
3. thin confluent epidermis fully grows to normal skin.
91
what are the differences between healing by first intention and second intention?
(mention wound edges, tissue loss, healing speed, granulation tissue, scar formation and give examples)
Wound edges:
1st- close together (e.g. sutured)
2nd- far apart, cannot be approximated
tissue loss:
1st- minimal
2nd- significant
healing speed:
1st- faster
2nd- slower
granulation tissue:
1st- minimal
2nd- extensive
scar formation:
1st- minimal
2nd- prominent
examples:
1st- surgical incision, small cuts
2nd- burns, ulcers, large open wounds
92
what are the steps in the healing cascade?
1. hemostasis
2. inflammation
3. proliferation
4. remodelling (only for repair)
93
describe what happens in haemostasis in the healing cascade
* hemostasis begins immediately after injury to stop blood loss.
* blood vessels constrict, and platelets aggregate at the wound site, forming a blood clot
94
describe what happens in inflammation in the healing cascade
neutrophils arrive first to kill bacteria, clear debris (e.g. dead cells)
95
describe what happens in proliferation in the healing cascade
* fibroblasts produce collagen and other components of the extracellular matrix (ECM) to support the forming tissue.
* angiogenesis occurs (under the influence of vascular endothelial growth factor), with new blood vessels forming to supply the wound with oxygen and nutrients.
* epithelialization: epithelial cells migrate across the wound to restore the skin barrier.
96
describe what happens in remodelling in the healing cascade
* the wound gradually strengthens as collagen fibres are rearranged and cross-linked.
* myofibroblasts help contract the wound, reducing scar size.
* eventually, scar tissue forms, and blood vessels decrease, leading to a stable wound.
97
Man aged 30 takes a large paracetamol overdose and doesn’t come to hospital for 2 days. He spends a few days on ICU with liver failure but then recovers.
What will be happening in his liver - resolution or repair?
Resolution
98
A child aged 3 fell off a climbing frame onto his hand, he fractured his clavicle. He has his arm in a sling for 4 weeks but won’t keep the sling on and moves his arm a lot.
What will be happening in his clavicle - resolution or repair?
Repair
99
what are the steps involved in the development of an atherosclerotic plaque?
1. damage to the endothelium
2. inflammatory response
3. fatty streat formation
4. plaque growth
5. plaque rupture or erosion
100
during the development of an atherosclerotic plaque what is damage to the endothelium caused by?
* hypertension
* chemicals from smoking
* high LDL cholesterol
101
explain the inflammatory response generated in the development of an atherosclerotic plaque
1. LDL cholesterol accumulates at the site of damage (in the tunica intima)
2. damaged endothelial cells express adhesion molecules (for diapedesis)
3. monocytes enter tunica intima via diapedesis
4. monocytes then release free radicals which oxidise the LDLs (Ox-LDL)
5. Ox-LDLs are effective at attracting more monocytes into the tunica intima
6. Monocytes differentiate into macrophages
7. macrophages phagocytose the Ox-LDL
102
explain the formation of fatty streaks in the development of an atherosclerotic plaque
1. as macrophages phagocytose the Ox-LDL the cytoplasm becomes filled with lipid droplets (as LDLs are filled with triglycerides
2. this gives them a foamyh appearance and are hence referred to as foam cell- foam cells release chemokines which attract more macrophages, amplifying inflammation
3. the fatty streak is the first visible sign of atherosclerosis and is a patch of dead foam cells (at the site of endothelial damage)
103
explain the growth of plaques in the development of an atherosclerotic plaque
1. foam cells cause smooth muscle cells from the media layer of the vessel migrate to the intima and start producing extracellular matrix proteins like collagen and elastin
2. these smooth muscle cells, along with the extracellular matrix, form a protective fibrous cap over the lipid core (cholesterol and foam cells)
3. the cap isolates the lipid core from the bloodstream, creating a more mature atherosclerotic plaque.
4. existing endothelium proliferates and forms new endothelium over the fibrous cap.
104
what are the layers of the tunica externa?
adventitia
105
what are the layers of the tunica media?
(outwards to inwards)
external elastic lamella and smooth muscle
106
what are the layers of the tunica intima?
(outwards to inwards)
internal elastic lamella
basement membrane
endothelium
107
what happens to the lipid core as the plaque becomes more advanced?
the lipid core becomes more necrotic as the plaque gets more advances and foam cells die
108
explain the rupture/ erosion of the plaque in the development of an atherosclerotic plaque
1. endothelial cells around the plaque get worn away, exposing the extracellular matrix proteins like collagen
2. blood exposure to collagen causes blood clots (platelet plug)
3. clots block blood flow and can lead to myocardial infarction or stroke (especially when they break off)
109
what are the accepted theories of how atherosclerosis happens?
* endothelial damage theory
* lipid accumulation theory
* hemodynamic forces theory
110
what is the endothelial damage theory?
endothelial damage leads to increased permeability, allowing lipids to accumulate in the vessel wall
111
what is the lipid accumulation theory?
lipid accumulation, particularly oxidised LDL, triggers inflammatory responses
112
what is the hemodynamic forces theory?
hemodnamic forces, particularly low shear stress and turbulent blood flow, are thorugh to contribute to the development of atherosclerosis by triggering endothelial damage.
113
are there any discredited theories about the triggers of atherosclerosis?
lipid insudation theory
114
what are the risk factors for atherosclerosis?
* High LDL cholesterol
* hypertension
* smoking
* diabetes mellitus
* obesity
* sedentary lifestyle
* diet
* excessive alcohol consumption
* age
* sex
* family history
115
what is the definition of apoptosis?
programmed cell death
116
what is the definition of necrosis?
traumatic cell death
117
what is the difference between apoptosis and necrosis?
apoptosis is a regulated, programmed process of cell death, allowing cells to die in a controlled manner without harming neighbouring cells
necrosis is the wholesale destruction of large numbers of cells by some external factor.
118
what are some clinical examples of necrosis?
* infarction due to loss of blood supply, e.g. myocardial infarction
* frostbite
* toxic venom from reptiles and insects
* pancreatitis
119
what happens after necrosis?
after necrosis all the body can do is try to clear up the mess by macrophages phagocytosing the dead cells and usually by replacing the necrotic tissue by fibrous scar tissue (unless the tissue can regenerate)
120
what are the different types of necrosis?
* liquefactive
* coagulative
* caseous
* fat necrosis
* fibrinoid necrosis
* gangrenous necrosis
121
what is liquefactive necrosis?
characterised by the dissolution of dead cells into a liquid viscous mass, often seen in brain infarcts and abscesses due to bacterial infections
122
what is coagulative necrosis?
involves the preservation of tissue architecture with cells death, typically occuring in hypoxic environments like myocardial infarctions
123
what is caseous necrosis?
exhibits a cheese-like appearance, commonly associated with tuberculosis infections where dead cells disintegrate but dont completely liquefy
124
what is fat necrosis?
results from the destruction of fat tissue, often due to pancreatic enzyme leakage in acute pancreatitis, leading to saponification (formation of chalky deposits)
125
what is fibrinoid necrosis?
involves immune-mediated vascular damage, resulting in bright pink fibrin-like deposits within vessel walls, commonly seen in vasculitis
126
what is gangrenous necrosis?
refers to tissue death due to severe ischemia, which can be "dry" (coagulative) or "wet" (liquefactive) if infected by bacteria.
127
describe the intrinsic pathway to activate apoptosis
* it's triggered by internal stress such as DNA damage or oxidative stress
* BCL2 family proteins prevent apoptosis
* BAX proteins trigger apoptosis
* apoptosis occurs due to a cascade of activated enzymes ending in caspases.
* macrophages clean up apoptosed cells
128
describe the extrinsic pathway to activate apoptosis
FAS ligand binds to FAS receptor (a type of 'death receptor')/ tumour necrosis factor (TNF) binds to TNF receptor (another type of 'death receptor')
another cascade of enzymes, ending in caspases activates apoptosis
129
how are lymphocytes which produce self antigens eliminated?
through the Extrinsic pathway of apoptosis
130
what is the extrinsic factor used for? give examples.
development- removal of cells during development, e.g. interdigital webs
cell turnover- removal of cells during normal turnover, e.g. in the intestinal villi where cells are replaced from below and apoptose at the tips
131
what is the extrinsic pathway of apoptosis used for in disease?
* cancer- cells in tumours dont apoptose when expected to, often dur to the mutation of the p53 protein (so it cannot detect DNA damage).
* HIV- HIV virus can induce apoptosis in CD4 T-helper cells which reduces their numbers enormously, producing an immunodeficient state.
132
what is the cytotoxic pathway of triggering apoptosis?
* NK cells and CD8+ cells release perforins to create pores
* granzymes enter cells and apoptose them
133
what are the different types of developmental disorders?
Congenital, inherited and acquired
134
what is a congenital developmental disorder? give examples
present at birth
E.g. spina bifida, cleft lip, septal defect (in the heart)
135
what is an inherited developmental disorder? give examples
caused by an inherited generic abnormality (may not manifest until later life)
e.g. cystic fibrosis, sickle cell anaemia, huntington's disease, downs syndrome
136
what is a acquired developmental disorder? give examples
caused by non-genetic environmental factors (may be congenital)
e.g. foetal alcohol syndrome (alcohol)
cerebral palsy (postnatal brain injury)
acromegaly (too much growth hormone- can be due to a tumour)
137
what are the main causes of inherited developmental disorders?
* mutations in single genes (mendelian inheritance
* mutations in multiple genes (polygenic inheritance)
* mutations in sex genes (autosomal inheritance)
* chromosomal abnormalities
137
what are the main causes of congenital developmental disorders?
* teratogens (alcohol, recreational drugs, radiation, etc.)
* nutritional deficiencies
* intrauterine factors (e.g. poor placental blood supply or maternal infections)
138
what are the main causes of acquired developmental disorders?
physical trauma
infections
environmental toxins
139
what is hypertrophy?
give an example
an increase in the size of a tissue caused by an increase in the size of the constituent cells
e.g. bodybuilding
140
what is hyperplasia?
give an example
an increase in the size of a tissue caused by an increase in the number of the constituent cells
e.g. enlarged prostate
141
what is atrophy?
give an example
decrease in the size of a tissue caused by a decrease in the number of the constituent cells or a decrease in their size.
E.g. alzheimer's disease
142
what is metaplasia?
give an example
A change in differentiate of a cell from one fully-differentiated cell type to a different fully-differentiated cell type.
e.g. barrett's oesophagus, change of columnar cells in bronchi to squamous due to smoking.
143
what is dysplasia?
give an example
an imprecise term for the morphological changes seen in cells (often epithelium) in the progression to becoming cancer (abnormal cell growth)
sometimes refers to developmental abnormality
e.g. bronchial epithelium in cigarette smokers: metaplasia from ciliated to squamous epithelium, then the development of dysplasia in the squamous epithelium.
144
what is a telomere?
a repetitive DNA sequence at the end of a chromosome that protects the chromosome's ends from becoming frayed or tangled.
145
how is telomere length inherited?
paternally
146
why do skin cells from older people divide less times in culture than those from younger people?
this happens because at each division, the telomere region at the end of the chromosomes shortens and eventually becomes so short that it is not possible for the chromosomes to divide
147
how do senescent cells die?
senescent cells are those that cannot replace themselves by dividing so they will die once they have accumulated a certain amount of damage
148
what factors can cause senescent cell death?
* cross linking of protiens
* loss of calcium influx controls
* damage to mitochondrial DNA
* loss of DNA repaid mechanism
* peroxidation of membranes
* free radical generation
* time-dependent activation of ageing and death genes
* telomere shortening
* accumulation of toxic by-products of metabolism
149
what is autophagy?
the removal of damaged organelles within a cell
150
how do the cellular mechanisms of ageing produce clinically apparent disease in skin?
wrinking of skin caused by UV-B light, causing cross liking of proteins, especially collagen in the dermis
151
how do the cellular mechanisms of ageing produce clinically apparent disease in the eyes?
cataracts are caused by UV-B light, causing cross-linking of proteins in the lens, causing opacity
152
how do the cellular mechanisms of ageing produce clinically apparent disease in bones?
loss of bone matrix predominantly in women after the menopause causes osteoporosis
153
how do the cellular mechanisms of ageing produce clinically apparent disease in the brain?
may be alzhiemers or vascular dementia, there are genetic factors that cause it.
154
how do the cellular mechanisms of ageing produce clinically apparent disease in muscle?
it causes a loss of muscle (sarcopenia)- may be the thing that prevents independent living in older people due to problems such as getting out of chairs and upstairs
155
how do the cellular mechanisms of ageing produce clinically apparent disease in the ears?
the hair cells in the cochlea do not divide so if they are damaged in high volumes they will die and not be replaced, eventually producing deafness.
156
what is a neoplasm?
a lesion resulting from the autonomous or relatively autonomous abnormal growth of cells which persists after the initiating stimulus has been removed (can be benign or malignant)
157
give examples of some benign neoplasms
* polyps
* sebaceous cysts
* fibroids
* adenoma, lipoma, chondroma
158
give some examples of malignant neoplasms
cancer
159
define carcinogenesis
the transformation of normal cells to neoplastic cells through permanent genetic alterations or mutations (applies to malignant neoplasms)
160
define oncogenesis
the transformation of normal cells to neoplastic cells (applied to benign and malignant neoplasms)
161
define carcinogens
agents known or suspected to cause cancer
162
define carcinogenic
describes the property of an agent to cause cancer
163
define oncogenic
describes the property of genes or factors to promote tumour formation
164
what are oncogenes?
genes that have the potential to cause cancer
165
what are oncogenic viruses?
viruses that cause cancer
166
what percentage of cancer risk is environmental?
85%
167
how do environmental agents cause cancer?
by damaging the DNA
168
what are some occupational/ behavioural risks of cancer?
lung cancer- smoking
bladder cancer- aniline dye and rubber industries
skin cancer- unprotected/ over exposure to UV
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what techniques do we use to identify carcinogens?
we look at:
* incidence of tummours in laboratory animals
* cells/ tissue cultures
* mutagenicity testing in bacterial cultures
170
why might the techniques we use to identify carcinogens not be accurate?
animals/ cultures may metabolise agents differently to humans
bacterial mutation may not- carcinogenicity
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what are the main classes of carcinogenic agents?
* Chemical
* viral- DNA and RNA
* Ionising and non-ionising radiation
* hormones
* parasites
* mycotoxins
* miscellaneous
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describe chemical carcinogenic agents
* 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
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what type of neoplams can polycyclic aromatic hydrocarbons cause?
what class of carcinogenic agents do they belong to?
what specific carcinogenic agents cause them?
Lung cancer
skin cancer
Chemical carginogens
Smoking
mineral oils
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what type of neoplams can aromatic amines cause?
what class of carcinogenic agents do they belong to?
what specific carcinogenic agents cause them?
bladder cancer
chemical carcinogens
rubber/ dye
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what type of neoplams can nitrosamines cause?
what class of carcinogenic agents do they belong to?
gut cancers
chemical carcinogens
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what type of neoplams can alkylating agents cause?
what class of carcinogenic agents do they belong to?
how high is the risk?
Leukemia
Chemical
Small risk
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describe viral carcinogenic agents
they cause approximately 10-15% of all cancers
most oncogenic viral infections don't cause cancer
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what are some DNA viruses that can cause cancer?
human herpesvirus 8- HHV8
epstein barr virus- EBV
hepatitis B virus- HBV
Human papillomavirus- HPV
Merkel cell polyomavirus- MCV
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what virus causes the kaposi sarcoma?
Human Herpesvirus 8- HHV8
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What cancers can Epstein Barr virus cause?
Burkitt lymphoma
nasopharyngeal carcinoma
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what virus causes hepatocellular carcinoma?
Hepatitis B virus- HBV
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what cancers can the human papillomavirus cause?
Squamous cell carcinomas of the cervix, penis, anus, head and neck
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what are some RNA viruses that can cause cancer?
Human T lymphotropic virus- HTLV-1
Hepatitis C virus- HCV
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what cancers does human T- lymphotrophic virus cause?
Adult T- cell leukemia
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what virus causes hepatocellular carcinoma?
Hepatitis C virus
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describe ionising and non- ionising carcinogenic agents
UV light:
* exposure to UVA or UVB increased risk of BCC, melanoma and SCC
* increased risk in throse with xeroderma pigmentosum
ionising radiation (long term effect):
* skin cancer in radiographers
* lung cancer in uranium miners
* thyroid cancer in urkranian children (chernobyl, 125 and 121 iodine)
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describe hormonal carcinogenic agents
Oestrogen- increase in mammary/ endometrial cancer
anabolic steroids: hepatocellular cancer
187
describe parasitic carcinogenic agents
Clonorchis sinensis- cholangiocarcinoma
schistosoma- bladder cancer
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describe mycotoxic carcinogenic agents
aflatoxin B1- hepatocellular carcinoma
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describe miscellaneous carcinogenic agents
- asbestos
- metals
190
how is ethnicity liked to carcinogenesis?
* increased oral cancer in India and SE asia (reverse smoking)
* reduced skin cancer in those with darker skin
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how is diet/ lifestyle liked to carcinogenesis?
* excess alcohol use increases risk of cancers of mouth, oesophagus, liver, colon and breast
* obesity increases risk of breast, oesophagus, colon and kidney cancers
* exercise reduces the risk of colon and breast cancer
* unprotected sex increases risk of HPV-related cancer
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how are constitutional factors (e.g. age, gender) liked to carcinogenesis?
* inherited predisposition
* incidence increases with age
* breast cancer in female to male- 200:1
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what are premalignant conditions?
identifiable local abnormality associated with increased risk of malignancy at that site, e.g. ulcerative colitis, undecended testes, colonic polyps
194
give an example of transplacental exposure
Diethylstilboestrol- increased risk of vaginal cancer
195
how do benign neoplasms cause morbidity and mortality
* exert pressure on adjacent structures
* obstruct flow
* produce hormones (as they are similar to the original tissue
* transform to malignant neoplasm
* anxiety
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how do malignant neoplasms cause morbidity and mortality
* destruction of adjacent tissue
* metastases
* blood loss from ulcers
* obstruction of flow
* produce hormones
* paraneoplastic effects
* anxiety and pain
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define the incidence of neoplastic disease
* 25% of population have neoplasia
* affects all ages
* an increased risk with age
* high mortality rate
* 20% of all deaths
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describe neoplastic cells
* derive from nucleated cells
* usually monoclonal
* growth pattern and synthetic activity related to parent cell
199
describe the neoplastic stroma
it is the supporting connective tissue within a tumour, composed of cells like fibroblasts, blood vessels and extracellular matrix, which are not cancerous themselves but are actively involved in the growth, invasion and progression of the cancerous cells within the tumour mass
200
what are the specific characteristics of neoplasia?
* uncontrolled cell proliferation
* loss of normal differentiation
* genetic instability
* avoidance of apoptosis
* angiogenesis
* invasiveness and metastases
* disorganised tissue architecture
* altered metabolism
* resistance to growth inhibition signals
201
describe uncontrolled cell proliferation as a specific characteristic of a neosplasm
* hallmark of benign and malignant tumour
* occurs due to mutations in genes which controlt he cell cycle such as oncogenes, e.g. Her2 and tumour suppressor genes e.g. p53
202
describe loss of normal differentiation as a specific characteristic of a neosplasm
* cells lose the specialised features of the normal tissue from which they originated
* lack of differentiation is known as anaplasia
203
describe genetic instability as a specific characteristic of a neosplasm
* accumulate mutations faster than normal cells
* this results from defects in the mechanisms of DNA repair or the regulation of cell devision (e.g. a mutation in the P53 gene or BRCA1/2)
204
describe the avoidace of apoptosis as a specific characteristic of a neosplasm
* evasion occur due to mutations in genes that regulare apoptosis, such as p53
* overexpression of anti-apoptotic proteins (e.g. BCL-2)
205
describe angiogenesis as a specific characteristic of a neosplasm
* tumour cells secrete vascular endothelial growth factor (VEGF) which causes grwoth of new blood vessels
* central necrosis due to rapid proliferation, angiogenesis is not fasgt enough to support new tumour cells
206
describe invasiveness and metastases as a specific characteristic of a neosplasm
specific to malignant neoplasms
207
describe disorganised tissue architecture as a specific characteristic of a neosplasm
results in irregularly shaped neoplasms
208
describe altered metabolism as a specific characteristic of a neosplasm
* increased metabolism to support growth and survival
* warburg effect- cancer cells increase uptake of glucose even in the presence of oxygen, more glycolysis occurs
209
how are benign tumours classified?
* non-cancerus
* remain localised
* grow slowly (low mitotic activity)
* do not invade surrounding tissues
* close resemblace to normal tissue
* necrosis and ulceration rare
* nuclear morphometry often normal
* growth on mucosal surfaces usually exophytic
210
how are borderline tumours classified?
* a non-cancerous tumour that forms in the tissue that covers an ovary
* can grow and spread but a lot more slowly than regular malignant neoplasms
211
how are malignant tumours classified?
* grow rapidly (increased mitotic activity)
* invade nearby tissues (invasive)
* metastasize
* variable resemblance to normal tissue
* poorly defined or irregular border
* hyperchromatic nucleo
* pleomorphic nuclei
* necrosis and ulceration common
* growth on mucosal surfaces often endophytic
212
what are the histological classifications of neoplasms?
* grade 1- tumour cells are similar to healthy cells
* grade 2- tumour cells are somewhat abnormal
* grade 3- tumour cells are very abnormal
* grade 4- tumour cells are the most abnormal and considered undifferentiated (most dissimilar to the normal cells)
213
what is a papilloma?
benign neoplasm of non-glandular, non-secretory epithelium, previx with the cell type of origin. e.g. squamous cell papilloma
214
what is an adenoma?
benign neoplasm of glandular or secretory epithelium, prefix with cell type of origin, e.g. thyroid adenoma
215
what is a carcinoma?
malignant epithelial neoplasm, prefix with epithelial cell type, e.g.:
adenocarcinoma (neoplasm of glandular epithelium)
cholangiocarcinoma (neoplasm of the bile ducts)
216
what is a lipoma?
benign neoplasm of adipocytes
217
what is a chrondroma?
benign neoplasm of cartilage
218
what is an osteoma?
a benign neoplasm of bone
219
what is an angioma?
benign neoplasm of blood vessels
220
what is a rhabdomyoma?
benign neoplasm of striated muscle
221
what is a leiomyoma?
benign neoplasm of smooth muscle
222
what is a neuroma?
benign neoplasm of nerves
223
what is a liposarcoma?
malignant neoplasm of adipocytes
224
what is a rhabdomyoscarcoma?
a malignant neoplasm of striated muscle
225
what is a leiomyosarcoma?
a malignant neoplasm of smooth muscle
226
what is a chondroscarcoma?
a malignant neoplasm of cartilage
227
what is an osteosarcoma?
a malignant neoplasm of bone
228
what is an angiosarcoma?
a malignant neoplasm of blood vessels
229
what is an anaplastic neoplasm?
where the cell type of origin cannot be determined the neoplasm is said to be anaplastic
230
what is a lymphoma?
malignant neoplasm of lymphocytes
231
what is a melanoma?
a malignant neoplasm of melanocytes
232
what is a leukemia?
malignant neoplasm of blood cells
233
what is a mesothelioma?
a malignant neoplasm of mesothelial cells
234
what is a myeloma?
malignant neoplasm of plasma cells
235
which -omas are not neoplasms
* granuloma
* mycetoma
* tuberculoma
236
name some epononymously named neoplasms?
burkitt lymphoma
ewing sarcoma
grawitz tumour
kaposi sarcoma
237
what is a teratoma?
benign or malignant tumour made of several types of tissue, e.g. hair, bone, teeth
238
what is a blastoma?
embryonal neoplasms/ neoplasms in precursor cells, e.g. fibroblasts
239
what is a carcinosarcoma?
mixed neoplasms
240
what is the TNM system?
T (tumour)- the size and extent of the primary tumur and how far it has invaded nearby tissues (1-4)
N (nodes)- the amount cancer has spread to nearby lymph nodes (0-3)
M (metastasis)- whether the cancer has spead to other parts of the body (0-1)
241
what is the difference between cancer invasion and cancer metastasis?
invasion- when cancer cells spread beyond the tissue where they first developed and grow into nearby healthy tissues
metastasis- when cancer cells have spread from its original location to other parts of the body (responsible for (90%) of deaths
242
what is the spectrum of cancer from normal to metastatic?
normal tissue, carcinoma in situ, invasive carcinoma, metastatic carcinoma.
243
what are the steps in the metastatic cascade?
1. invasion and migration
2. angiogenesis and intravasation
3. survival in circulation and attachment to the endothelium
4. extravasation and colonisation
244
what is invasion and migration in the metastatic cascade?
epithelial to mesenchymal transition (EMT): process whereby tightly- interacting and immotile epithelial cells acquire the phenotype of loosely adherent (non-stickly) and motile mesenchymal cells, acquiring the ability to move and invade.
245
what is angiogenesis and intravasation in the metastatic cascade?
angiogenesis:
* tumour growth results in an increased demand for oxygen. the tumour cells secrete mediators which recruit blood vessels to supply the tumour, e.g. VEGF (hypoxic signalling).
* the new blood vessels tend to be disorganised and fragile (bleeding is common, hence why seeing blood in stool is a symptom of bowel cancer)
intravasation:
* cancer spreads into the new disorganised blood vessels which have been brough about by VEGF signalling. it is the process by which cancer cells break through the endothelium and reach the bloodstream.
246
what is survivial in circulation and attachment to the endothelium in the metastatic cascade?
* shear forces and the immune system will be removing some cancer cells
* 10% -30% of patients with early stage cancer have cancer cells detecable in the bloodstream.
247
what is extravasation and colonisation in the metastatic cascade?
extravasation:
cancer cells leave blood supply and enter surrounding tissues. mesenchymal to epithelial transition (opposite of EMT) so circulating tumour cells stick to tissue
colonisation:
cells either divide or enter dormant stage
248
what are some exampes of cancers that start after they enter the dormant state?
* melanoma
* renal cell carcinoma
* breast cancer
249
what is CTC?
circulating tumour cells
250
what are some routes of cancer spread?
* lymphatics (preferred by carcinomas)
* blood vessels (preferred by sarcomas)
* Nerves
* Transcoelomic (a route of tumour metastasis across a body cavity, such as the pleural, pericardial or peritoneal cavity)
* iatrogenic (via surgery or other medical procedures)
251
which cancers tend to produce metastases in bone?
* prostate
* breast
* lung
* kidney
* thyroid
252
what are the hallmarks of cancer?
the hallmarks of cancer are a set of biological capabilities that cancer cells acquire during tumour development. e.g.:
* evading growth suppressorts
* non-mutational epigenetic reprogramming
* avoiding immune destruction
* enabling replicative immortality
* tumour-promoting inflammation
* polymorphic microbes
* activating invasion and metastasis
* inducing or accessing vasculature
* senescent cells
* genome instability and mutation
* resisting cell death
* deregulating cellular metabolism
* unlocking phenotypic plasticity
* sustaining proliferative signalling
253
what is the full form of HER2 and what is it?
HER2 (human epidermal growth factor receptor 2) is a gene that can play a role in the development of breast cancer
254
by what percentage is the HER2 gene amplified in breast cancers?
20%- 30%
255
what is the amplified HER2 gene associated with?
* large size
* high grade
* negative oestrogen receptor status
256
what does negative oestrogen receptor status mean?
it means that the cancer cells do not have oestrogen receptors on their surface, it means that the cancer is less likely to respond to hormone therapy aimed at blocking oestrogen
257
how does conventional chemotherapy work?
it usually hits normal cells which are dividing, so it's not selective for tumour cells
it causes myelosuppression (reduces bone marrow activity), hair loss, diarrhoea
258
what type of tumours is chemotherapy good for?
it's good for fast dividing tumours:
* germ cell tumours of testis
* acute leukaemias
* lymphomas
* embryonal paediatric tumours
* choriocarcinoma (cancer of the placenta)
259
how does radiation therapy work?
radiation therapy uses high-energy rays or particles to damage the DNA of cancer cells, causing them to die or lose their ability to divide.
normal cells have a better ability to repair DNA damage.
