Introduction to Clinical Sciences (detailed) Flashcards
Probs too much info (247 cards)
1
Q
Def: Acute inflammation
A
Initial and often transient series of tissue reactions to injury - may last from a few hours to a few days
2
Q
Def: Chronic inflammation
A
Prolonged inflammatory reactions involving a progressive change in type of cell present
3
Q
List the main symptoms of inflammation (4)
A
Heat, Redness, Swelling, Pain, (loss of function also a characteristic)
4
Q
List the 4 stages of Neutrophil polymorph emigration
A
Margination of neutrophils
Adhesion of neutrophils
Neutrophil emigration
Diapedesis
5
Q
Def: Neutrophil polymorph emigration
A
Accumulation of neutrophil polymorphs within the extracellular space
6
Q
Describe the margination of neutrophils
A
- Normal circulation - cells confined to axial flow (central)
- Due to loss of fluid in inflammation plasma viscosity increases and flow decreases
- Neutrophils able to flow in plasmatic zone next to endothelial cells
7
Q
Describe the adhesion of neutrophils
A
○ Known as pavementing
○ Random contact with endothelium results in interactions between WBC and endothelial cells
○ Occurs only in venules
○ Adhesion molecules made more active by chemical inflammatory mediators
8
Q
Describe neutrophil emigration
A
○ Migrate through the walls of venules and small veins
○ Insert pseudopodia between endothelial cells and move through the gap and through the basal lamina into the vessel wall
9
Q
Name the chemical mediators involved in vascular dilatation
A
Histamine, Prostaglandin E2, Nitric oxide, PAF (platelet-activating factor), VIP (vasoactive intestinal peptide)
10
Q
Name the chemical mediators involved in increased vascular permeability
A
Immediate transient: Histamine
Prolonged: Bradykinin, Nitric oxide, C5a, Leukotriene B4 and PAF
Immediate sustained: Severe direct vascular injury
Delayed prolonged: Endothelial cell injury e.g. x-rays, bacterial toxins
11
Q
Name the chemical mediators involved in adhesion of leukocytes to endothelium
A
IL-8, C5a, Leukotriene B4, Il-1 and TNF-a
12
Q
Name the chemical mediators involved in neutrophil polymorph chemotaxis
A
Leukotriene B4 and IL-8
13
Q
Which cells release histamine
A
Basophils and mast cells
14
Q
What induces the release of histamine from basophils and mast cells
A
C5a, C3a and lysosomal proteins
15
Q
Name causes of inflammation (6)
A
- Hypersensitivity reactions
- Microbial infections
- Physical agents
- Chemicals
- Bacterial toxins
- Tissue necrosis
16
Q
Give some examples of physical agents resulting in inflammation
A
Ionising radiation, Heat, Cold, Trauma
17
Q
Give some examples of chemicals resulting in inflammation
A
Corrosives, Acids, Alkalis, Reducing agents
18
Q
Name the plasma factors (4)
A
Complement factors
Kinins
Coagulation factors
Fibrinolytic system
19
Q
What is the basic function of the complement system
A
Removes and destroys pathogens via opsonisation or by direct lysis
20
Q
What are the 3 pathways of the complement system
A
Classical
Alternative
Lectin
21
Q
How is the classical pathway (complement system) activated
A
Antibody binds to bacterial antigens -> classical pathway activated -> generates C3b (opsonising properties
22
Q
How is the alternative pathway (complement system) activated
A
Bacterial lipopolysaccharides detected -> alternative pathway activated -> C3b generated
23
Q
What do macrophages do in inflammation
A
- Secrete cytokines IL-1 and TNF-a
- Cause endothelial, fibroblast and epithelial cells to secrete MCP-1
- Predominate in later stages
- Responsible for clearing tissue debris, damaged cells and digestion of inflammatory exudate
24
Q
What is MCP-1
A
Monocyte chemoattractant protein 1 also known as CCL2 - attracts monocytes, T memory cells and dendritic cells to site of inflammation
25
How is exudate drained
Lymph vessels become dilated and drain fluid to prevent extensive tissue oedema
26
Describe the process of phagocytosis
* Adhesion of pathogen to cell surface -> opsonisation
* Ingestion of pathogen - pseudopodia surround and fuse into a phagosome
* Lysosome fusion with phagosome to form a phagolysosome
* Intracellular killing
27
Basic description of oxygen-dependent intracellular killing
Reactive oxygen species like hydrogen peroxide react with myeloperoxidase in the presence of a halide to produce a potent microbicidal agent
28
Basic description of oxygen independent intracellular killing
Include lysozymes (muramidase) and lactoferrin
29
List the benefits of inflammation (5)
- Destruction of invading microorganisms and walling off of abscess cavity, preventing infection spread
- Dilution and removal of toxins by lymph drainage
- Entry of antibodies into exudate allows killing of pathogens
- Fibrin formation from exuded fibrinogen impedes pathogen movement and serves as a matrix for formation of granulation tissue
- Stimulation of immune response via drained exudate to lymph nodes -> antigens detected
30
List the limitations of inflammation (5)
- Disease -> abscess in the brain acts as a space-occupying lesion, compressing surrounding structures
- Fibrosis resulting from chronic inflammation distorts and alters the function of tissues
- Digestion of normal tissues due to collagenase and protease release
- Swelling is dangerous in enclosed spaces such as the cranial cavity -> raises pressure to blood flow is restricted, possibly leading to ischaemia
- Hypersensitivity reactions (e.g. anaphylactic shock)
31
List the 4 main outcomes of inflammation
- Resolution
- Suppuration
- Organisation
- Progression to chronic inflammation
32
Describe resolution of inflammation
Tissue completely returns to normal after episode of acute inflammation.
- Minimal cell death
- Good local vascular drainage
- Occurs in organ capable of regeneration
- Rapid destruction of causal agent
33
Describe suppuration and the outcomes it can have
Formation of pus:
- Pus surrounded by pyogenic membrane
- Abscess (collection of pus)
- Bacteria in the membrane is inaccessible to antibodies and antibiotic drugs
- Empyema - pus filled socket in hollow organ created by the fusion of an outflow tract by fibrin
34
Describe conditions that favour organisation after inflammation
Replacement of normal tissues with granulation tissue
- Lots of fibrin formed (enzymes not able to remove all)
- Tissue becomes necrotic or fibrous tissue not easily digested
- Exudate not removed or discharged
35
Describe what happens in organisation (inflammation) (4)
- New capillaries grow into exudate
- Macrophages migrate
- Fibroblasts proliferate under influence of TGF-b
- Defect filled by ingrowth of granulation tissue
- Granulation tissue produces collagen, forming a fibrous scar
36
Describe progression to chronic inflammation
- Causative agent not removed
| - Cell exudate changes composition
37
What is the change in cell exudate in progression to chronic inflammation
Instead of neutrophil polymorphs there are lymphocytes, macrophages, multinucleate giant cells and fibroblasts
38
3 main responses in acute inflammation
Increased vessel dilatation
Increased vascular permeability
Formation of exudate
39
What does release of lysosomal products result in
- Damage to local tissues by proteolysis (elastase, collagenase)
- Activates coagulation factor XII
- Attracts other leukocytes
- Some increase vascular permeability and others are pyrogens (induces systemic fever by acting on the hypothalamus)
40
What is the role of the mast cell in acute inflammation
- Stimulated by C3a/C5a
- Release preformed inflammatory mediators like histamine
- Metabolise arachidonic acid into leukotrienes, prostaglandins and thromboxanes
41
Descriptive terms for inflammation (5)
- Serous (lots of fluid release)
- Suppurative (purulent)
- Membranous
- Pseudomembranous
- Necrotising (gangrenous)
42
Name some systemic effects of inflammation (5)
- Pyrexia
- Constitutional symptoms
- Reactive hyperplasia of the reticuloendothelial system
- Haematological changes
- Amyloidosis
43
How is pyrexia induced in acute inflammation
- Stimulated by phagocytosis, endotoxins and immune complexes
- Neutrophil polymorphs and macrophages produce endogenous pyrogens (of which IL-2 ha the greatest effect
- Pyrogens act on the hypothalamus to set thermoregulatory mechanisms at a higher temperature
44
What are the constitutional symptoms of acute inflammation
- Malaise
- Anorexia
- Nausea
- Weight loss (negative nitrogen balance due to energy required to produce inflammatory mediators)
45
Describe reactive hyperplasia of the reticuloendothelial system
- Local or systemic lymph node enlargement
| - Splenomegaly is found in certain specific infections e.g. malaria and infectious mononucleosis
46
What are the haematological changes seen in acute inflammation
Increased levels of WBC
- increased neutrophils seen in pyogenic infections and tissue destruction
- Increased eosinophils in allergic and parasitic infection
- Increased lymphocytes seen in chronic infection and viral infections
- Increased monocytes seen in certain bacterial infections e.g. TB and typhoid
Anaemia may result due to blood loss into inflammatory exudate or haemolysis due to bacterial toxins
47
Describe amyloidosis
Long-standing chronic inflammation may cause amyloid to be deposited into various tissues, resulting in secondary amyloidosis
e.g. rheumatoid arthritis, TB, bronchiectasis
48
What is amyloid
Abnormal protein that builds up in organs/tissues and can eventually lead to their failure
49
Which cells predominate in chronic inflammation
Lymphocytes
Plasma cells
Macrophages
50
Name the types of chronic inflammation (4)
- Primary chronic inflammation
- Transplant rejection
- Progression from acute inflammation
- Recurrent episodes of acute inflammation
51
Describe primary chronic inflammation and give some examples
Where there is no initial phase of acute inflammation
| - TB, Asbestos fibres, Rheumatoid arthritis, Crohn's disease
52
Describe granulomatous inflammation
Immune system attempts to wall off substance but is unable to eliminate it, forming a granuloma
53
What is a granuloma
Collection of epithelioid histiocytes - stationary phagocytic cell found in tissue
54
Def: Angiogenesis
Formation of new blood vessels
55
Which cells are derived from monocytes (10)
```
Connective tissue histiocyte
Alveolar macrophage
Peritoneal macrophage
Kupffer cell
Melanophage of skin
Lipophage
Osteoclast
Microglial
Specialised histiocyte e.g epithelioid cell
Histiocytic giant cell
```
56
What changes does a macrophage undergo as they migrate into an area of inflammation (5)
Increase in size, protein synthesis, mobility, phagocytic activity, and content of lysosomal enzymes
57
Give some examples of cytokines produced by macrophages (6)
Interferon alpha and beta
IL-1, 6, 8
Tumour necrosis factor alpha (TNF-a)
58
What stain is used to identify TB and what colour does is turn
Ziehl-Neelsen stain goes bright red
59
List characteristics of epithelioid histiocytes
- Histologically similar to epithelial cells
- Large vesicular nuclei
- Plentiful eosinophilic cytoplasm
- Elongated
- Arranged in clusters
- Little phagocytic activity
- Secretory function (inc. ACE)
60
What is caseous necrosis
Tissue maintains cheese-like appearance - soft and white
61
When do histiocytic giant cells form
- Accumulation of particulate matter indigestible by macrophages
- Foreign particles too large to be ingested by one macrophage
62
List some characteristics of langerhans giant cells (2)
- Horseshoe arrangement of peripheral nuclei at one pole of cell
- Seen in TB and other granulomatous conditions
63
Describe healing by first intention
* Small blood vessels occluded by thrombosis
* Fibrin locally deposited binds sides of the wound
* Coagulated blood on the surface forms a scab keeping the wound clean
* Capillaries proliferate and fibroblasts secrete collagen as they migrate into fibrin network
* After ~ 10 days repair is sufficient enough for removal of suture
64
Describe healing by second intention (tissue loss)
* Phagocytosis to remove any debris
* Granulation tissue to fill in lesions and repair lost specialised tissue
* Epithelial regeneration to cover the surface
* Timescale depends on size of defect and final cosmetic result depends on how tissue loss there has been
65
Def: Atheroma
the build up of materials that adhere to arteries (fat, cholesterol, calcium, connective tissue, inflammatory cells). Can lead to stenosis of the arteries, resulting in atherosclerosis
66
Describe the pathogenesis of an atheroma (pt.1)
- Endothelial damage due to irritants
- Cholesterol collects in endothelium forming fatty streaks
- Cholesterol oxidised, activating an inflammatory response
- Monocytes migrate to area of damage and transform into macrophages
- Macrophages engulf large volumes of cholesterol, undergo apoptosis and become foam cells
- Foam cells release cytokines and growth factors, attracting more monocytes
67
Describe pathogenesis of an atheroma (pt.2)
- Smooth muscle cells migrate into the plaque due to platelet derived growth factor and secrete elastin and collagen, forming a fibrous cap
- Presence of foam cells stimulates smooth muscle cells to secrete calcium - hardens the plaque
68
What secretes growth factors
Platelets, injured endothelium, macrophages and smooth muscle cells
69
List risk factors for atherosclerosis
- Hypercholesterolaemia
- Smoking
- Hypertension
- Diabetes
- Male
- Increasing age
70
Def: fatty streak
Flat or slightly elevated yellow lesion in an artery wall containing intracellular accumulation of lipids
71
What does a fibrous cap contain
Smooth muscle cells, macrophages, lymphocytes, foam cells, collagen, elastin
72
List 4 clinical manifestations of an atheroma
- Lumen narrowing due to plaque stenosis
- Acute atherothrombotic occlusion
- Embolisation of distal arterial bed
- Ruptured abdominal atherosclerotic aneurysm
73
Outcomes of lumen narrowing
- Reversible tissue ischaemia (especially during exercise)
- Ischaemic pain may develop at rest
- Large intraplaque haemorrhage may increase rate of stenosis
74
Describe acute atherothrombotic ischaemia
- Plaque rupture exposes highly thrombogenic material - collagen and elastin
- Activation of coagulation cascade and thrombotic occlusion
- Total occlusion -> irreversible ischaemia leading to infarction
75
Why are small infarctions in the heart dangerous
Can lead to dangerous arrhythmias
76
Def: thrombosis
The solidification of blood contents that forms within the vascular system during life
77
When does a thrombus form
A pathological thrombus forms when there is an imbalance between natural coagulant and anticoagulant factors and the coagulation and fibrinolytic system
78
Name the 3 components of Virchow's triad
- Changes in vessel wall
- Changes in blood flow
- Changes in blood constituents
79
Describe normal blood flow
Laminar. Cells flow in the centre of the lumen and endothelial cells are not sticky
80
Describe pathogenesis of thrombosis
- Artery is narrowed and blood becomes turbulent
- Results in damage to endothelial cells and collagen is exposed
- Stimulates coagulation cascade
81
Describe the extrinsic pathway in coagulation cascade
○ TF activates VII to VIIa, forming a complex which then activates X to Xa (also activates IX to IXa which goes on to activate X through the intrinsic pathway)
○ Xa activates prothrombin to thrombin which activates fibrinogen to fibrin
○ Thrombin activates XI, V (cofactor with Xa), and VIII
82
Describe the intrinsic pathway in the coagulation cascade
○ XII activated by contact with collagen fibres
○ XIIa catalyses activation of XI
○ XIa catalyses activation of IX
○ IXa catalyses activation of X
83
Where does venous thrombosis usually occur
- Valves -> produce a natural degree of turbulence and can be damaged by trauma, stasis or occlusion
- Atheromas don't form in veins due to low BP
84
When does venous thrombosis usually occur
- Can be in young active individuals with no predisposing factors
- If BP drops (due to surgery, following MI) blood cells more likely to touch damaged vessel walls
- Immobilisation -> venous return relies on muscle contractions
85
4 fates of thrombi
- Resolved (fibrinolytic system dissolves it)
- Organisation (macrophages clear thrombus and fibroblasts replace it with collagen. scar forms and narrowed lumen)
- Recanalisation (capillaries grow through thrombus and fuse to form larger vessels - blood flow restored)
- Embolisation (fragments of thrombus break off into circulation)
86
Def: embolus
Mass of material in the vascular system able to lodge in a vessel and block its lumen
87
Types of embolus (5)
- Thrombus (most common)
- Air
- Cholesterol crystals
- Tumour amniotic fluid (pregnant women with rapid labour)
- Fat
88
Result of a small pulmonary embolism
- Lysed within the lung, unnoticed
- Organised and permanent -> small respiratory deficiency
- Accumulation over time may cause idiopathic pulmonary hypertension
89
Result of a large pulmonary embolism
- Acute respiratory and cardiac problems (may resolve with or without treatment)
- Symptoms = chest pain and shortness of breath
- Lung function impaired and patients more likely to have another embolism from the same source
90
Result of a massive pulmonary embolism
- Sudden death
| - Usually from long thrombi from DVT
91
Where do most systemic emboli originate from
The heart and atherosclerotic plaques
92
How do thrombi form in the heart
- Cardiac muscle dies in MI and collagen left exposed to circulating platelets
- AF -> blood stagnates in atria so thrombi form and when natural rhythm is re-established fragments may break off
93
Def: ischaemia
Reduction in the blood flow to a tissue or part of the body due to constriction or occlusion of the blood vessels supplying it
94
Extent of ischaemia depends on ....
- Duration of ischaemic period
| - Metabolic demands of the tissue
95
Def: infarction
The death of part or the whole of an organ that occurs when the artery supplying it becomes obstructed
96
Supply of an organ by only 1 artery
End arterial supply
97
Which organs have dual arterial supply
Liver - Portal hepatic vein and hepatic artery
Lungs - Pulmonary veins and bronchial arteries
Brain - Circle of Willis
98
Describe the pathology of reperfusion injury
| ????????
- During ischaemia transport mechanisms across the cell membrane are disrupted
-
99
Def: gangrene
Tissue necrosis where whole areas of a limb or region of the gut have their arterial supply cut off and large areas of mixed tissue die in bulk
100
Describe dry gangrene
Tissue dies and is mummified, healing occurs above it. Dead area drops off eventually - sterile process
101
Describe wet gangrene
Bacterial infection supervenes as a secondary complication. Gangrene spreads proximally and patient dies from sepsis
102
Describe pathology of disseminated intravascular coagulation
- Balance of thrombotic and thrombolytic mechanisms disturbed
- Thrombosis activated without effective counterbalance
- Small thrombi form throughout the body
- This causes bleeding in other areas of the body because clotting factors have been used up
103
Def: watershed areas
Tissue at the interface between adjacent territories supplied by 2 different arteries. Prone to infarction if there is impairment of blood/oxygen supply
104
Give 3 examples of watershed areas
1. Splenic flexure between inferior and superior mesenteric
2. Cerebral hemispheres at the interface between major cerebral arteries
3. Myocardium between tissue supplied directly by ventricles and coronary arteries
105
Name areas vulnerable to ischaemia and infarction
- Watershed areas
| - Tissue supplied by portal system
106
Name some areas supplied by portal vasculature
- Anterior pituitary receives blood from hypothalamus
- Renal tubular system receives blood from glomerular capillaries
- Parts of exocrine pancreas and receive blood already supplying the islet of Langerhans cells
107
List 5 other causes of ischaemia and infarction
1. Spasm
2. External compression
3. Steal
4. Hyperviscosity
5. Vasculitis
108
Describe pathology of spasm in ischaemia and infarction
- Transient arterial narrowing
- Can be due to decrease in nitric oxide production by vascular endothelium (cell injury or loss)
- Spasm of coronary arteries can lead to angina
109
Describe pathology of external compression in ischaemia and infarction
- Vessels partially or totally occluded by external compression
- intentionally done in surgery by ligation to prevent haemorrhage
- Veins more susceptible due to thin wall and low intraluminal pressure
- Common in strangulated hernia, testicular and ovarian torsion
110
Describe pathology of steal in ischaemia and infarction
- Blood diverted 'stolen' from a vital territory
- Atheroma causes blood to be diverted to competing area
- Tissue distal to the atheroma becomes ischaemic
111
Describe pathology of hyperviscosity in ischaemia and infarction
- Most impact in small vessels
| - Can be due to plasma cell tumour - abnormally high conc of antibodies
112
Describe pathology of vasculitis in ischaemia and infarction
- Inflammation of vessel wall narrows the lumen and increases chance of thrombus formation
113
Def: TIA
Transient ischaemic attack = a stroke that lasts for <24 hours and is associated with full recovery
It is a risk marker for cerebral infarction
114
Causes of cerebral infarction (
1. Atheroma in intra/extracranial arteries -> arterial thrombosis
2. Embolic arterial occlusion
3. Head injury -> hypoxia, vascular occlusion/rupture
4. Subarachnoid haemorrhage
5. Generalised arterial disease (e.g. vasculitis)
6. Critical reduction of cerebral blood flow
7. Critical reduction of arterial oxygenation
8. Venous thrombosis
115
What is a subarachnoid haemorrhage caused by (6)
1. Spontaneous rupture of saccular aneurysm in circle of Willis (most common)
2. Trauma
3. Hypertensive haemorrhage
4. Vasculitis
5. Tumours
6. Coagulation disorders
116
Def: apoptosis
Programmed cell death
117
List inhibitors of apoptosis (4)
1. Growth factors
2. Extracellular matrix
3. Sex steroids
4. Some viral proteins
118
List inducers of apoptosis (8)
1. Growth factor withdrawal
2. Loss of matrix attachment
3. Glucocorticoids
4. Some viruses
5. Free radicals
6. Ionising radiation
7. DNA damage
8. Ligand binding at 'death' receptors
119
What role to Bcl-2 and Bax have in apoptosis
- Bcl-2 inhibits factors inducing apoptosis and Bax-Bax dimers enhance apoptotic stimuli
- Ratio determines cell susceptibility to apoptotic stimuli
120
Describe the intrinsic pathway of apoptosis
- Responds to growth hormone withdrawal and biochemical stress
- DNA damage = stress
- p53 induces cell cycle arrest and induces apoptosis via Bcl-2 family activation
121
Describe the extrinsic pathway of apoptosis
- Ligand binding death receptors
- Binding promotes clustering of receptor molecules on the cell surface and initiates signal transduction cascade
- Activation of caspases
122
Execution phase of apoptosis
- pro-caspases activated by intrinsic/extrinsic pathway
- These are initiator caspases that cleave other pro-caspases
- Activated caspases cause degradation of many targets
- Cells phagocytosed immediately or fragment into apoptotic bodies which are phagocytosed later
123
Give some examples of apoptosis in disease (3)
- AIDs -> HIV proteins activate CD4 on uninfected T helper cells (induces apoptosis) - immunodepletion and dysfunction
- Neurodegenerative disorders
- Anaemia of chronic disorders
124
Def: Necrosis
Traumatic cell death which induces inflammation and repair
125
Describe coagulative necrosis
- Most common form and occurs in most organs
- Proteins coagulate and metabolic activity ceases
- Macrophages digest dead cells
- Necrotic tissue evokes inflammatory response
126
Describe liquifactive/colliquative necrosis
- Occurs in the brain
| - Lack of supporting stroma means necrotic neural tissue liquifies
127
Describe caseous necrosis
- Dead tissue is structureless like soft cheese
| - Characteristic in TB
128
Describe gangrene (necrosis)
- Rotting of tissues due to bacterial infection (especially clostridia)
- Tissue appears black due to iron sulfide released from degraded haemoglobin
129
Def: atrophy
Decrease in the size of a tissue cause by a decrease in size of individual cells or a decrease in number of constituent cells
130
3 pathological manifestations of atrophy
- Decreased function (immobilised limb due to cast -> muscle atrophy)
- Loss of innervation of a muscle
- Lack of nutrition (atrophy of adipose tissue, gut and pancreas)
131
What is the response of an individual cell to increased functional demand
Increase size by hypertrophy, hyperplasia, or both
132
Def: hypertrophy
Increase in cell size without cell division
133
Give 2 examples of hypertrophy
- In athletes: skeletal muscles due to increased activity and in left ventricle due to sustained outflow resistance
- Uterine smooth muscle at puberty and pregnancy (oestrogen)
134
Def: hyperplasia
Increase in cell number by mitosis
135
Give 2 examples of hyperplasia
- Living at high altitudes stimulates bone marrow hyperplasia (inc. erythropoietin)
- Benign/cancerous hyperplasia of prostate smooth muscle
136
Def: dysplasia
Imprecise term for the morphological changes seen in cells in the progression to becoming cancer. Also refers to lack of development
137
Def: metaplasia
The change in differentiation of a cell from one fully-differentiated cell type to a different fully-differentiated cell type
138
3 examples of metaplasia
Metaplasia occurs as a result to change in cell environment
1. Smoking - ciliated epithelium in the trachea transforms to squamous epithelium
2. Stone blocking - epithelium in salivary glands and pancreas + bile ducts transforms to squamous epithelium
3. Barrett's oesophagus - prolonged exposure to stomach acid changes squamous epithelium to columnar epithelium
139
Def: telomere
Non-coding section of randomly repetitive DNA at the tip of each chromosome
140
What is the significance of telomeres in ageing
- Telomeres not fully copied in DNA replication so shorten with each divide
- Eventually shorten to the extent that DNA polymerase is unable to engage
141
Where can telomerase be found
Germ cells and embryos
142
Def: sarcopaenia
Muscle loss due to ageing
143
When does sarcopaenia start and accelerate
Starts around 40, accelerates around 80
144
What is sarcopaenia caused by (basic)
Decreased growth hormone and testosterone and increased catabolic cytokines
145
Give 6 changes due to ageing and their causes
1. Deafness - hair cell loss
2. Senile dementia - brain atrophy (nerve cells unable to replicate)
3. Cataracts - UV light damage that cross links proteins in the eye
4. Osteoporosis - brittle bones due to oestrogen, vit D and calcium deficiency in early life
5. Dermal elastosis - wrinkling caused by UV
6. Impaired immunity - immunological changes result in lowered production of immune cells
146
Def: carcinogenesis
The transformation of normal cells to neoplastic cells through permanent genetic alterations or mutations. Only refers to malignant neoplasms
147
Def: neoplasm
A lesion resulting from the autonomous or relatively autonomous abnormal growth of cells which persists after the initiating stimulus has been removed
148
Def: neoplasia
The presence or formation of a new, autonomous, abnormal, persistent growth
149
Where can't neoplasm arise from
Erythrocytes (no nucleus so no DNA to mutate)
150
Def: tumour
Any abnormal swelling
151
4 types of tumour
1. Neoplasm
2. Inflammation
3. Hypertrophy
4. Hyperplasia
152
How can tumours be classified
By behaviour and histologically
153
5 ways benign tumours can cause morbidity/mortality
1. Pressure on adjacent structures
2. Obstruction of fluid
3. Production of hormone (thyroid tumour)
4. Transformation into malignant tumour
5. Anxiety and stress (patient hears tumour = cancer)
154
7 ways malignant tumours can cause morbidity/mortality
1. Pressure on and destruction of adjacent tumours
2. Formation of secondary tumours
3. Blood loss from ulcerated surfaces
4. Obstruction of fluid
5. Hormone production
6. Paraneoplastic effects resulting in weight loss and debility
7. Anxiety and pain
155
Growth rate of malignant tumours
Rapid
156
Nuclear morphology of malignant tumour
- Enlarged
- Hyperchromatic (stains darkly)
- Irregular outline
- Multiple nucleoli
- Pleomorphic (vary in size and shape)
157
Describe the border of a benign tumour
Often circumscribed (restricted within limits) or encapsulated
158
Describe the border of a malignant tumour
Often poorly defined or irregular
159
Direction of growth of benign tumours
Often exophytic
160
Direction of growth of malignant tumours
Often endophytic (invasive inwards direction of growth)
161
Def: histogenesis
The specific cell or origin of a tumour
162
Def: tumour grade
An assessment of tumour's degree of malignancy or aggressiveness
163
Factors to assess in tumour grading
1. Mitotic activity
2. Nuclear size (hyperchromasia & pleomorphism)
3. Degree of resemblance to the origin tissue
164
Def: tumour stage
Extent of a tumour's spread determined by histopathological and clinical examination
165
What are the 3 component of the TNM tumour grading system
Tumour size
Node status
Metastases
166
What is T(NM)
Primary tumour size
Number given that assesses the size of tumour and the organ harbouring it
Large number = large tumour
167
What is (T)N(M)
Lymph node status
| Number denotes the number of lymph nodes or groups of nodes containing metastases
168
What is (TN)M
Anatomical extent of metastases
169
Nomenclature: benign non glandular, non secretory epithelium
Papilloma
170
Nomenclature: benign glandular or secretory epithelium
Adenoma
171
Nomenclature: Malignant epithelium
Carcinoma
172
Nomenclature: Malignant glandular epithelium
Adenocarcinoma
173
Benign adipocyte tumour
Lipoma
174
Benign striated muscle tumour
Rhabdomyoma
175
Benign smooth muscle cell tumour
Leiomyoma
176
Benign cartilage tumour
Chondroma
177
Benign bone tumour
Osteoma
178
Benign vascular tumour
Angioma
179
Benign nerve tumour
Neuroma
180
Malignant adipocyte tumour
Liposarcoma
181
Malignant striated muscle tumour
Rhabdomyosarcoma
182
Malignant smooth muscle tumour
Leiomyosarcoma
183
Malignant cartilage tumour
Chondrosarcoma
184
Malignant bone tumour
Osteosarcoma
185
Malignant vascular tumour
Angiosarcoma
186
Malignant nerve tumour
Neurosarcoma
187
3 -oma that are not neoplasms
1. Granuloma - chronic inflammation
2. Mycetoma - fungus in the body
3. Tuberculoma - mass of TB
188
Malignant neoplasm of melanocytes
Melanoma
189
Malignant tumour of mesothelial cells
Mesothelioma
190
Malignant neoplasm of lymphoid cells
Lymphoma
191
Burkitt's lymphoma
B-cell lymphoma caused by Epstein-Barr virus
192
Ewing's sarcoma
Malignant tumour of the bone
193
Hodgkin's lymphoma
Malignant neoplasm characterised by presence of Reed-Sternberg cells
194
Kaposi's sarcoma
Malignant neoplasm derived from vascular endothelium, commonly associated with AIDs
195
Def: Teratoma
Neoplasm of germ cell origin that forms cells representing all 3 germ cell layers of the embryo (endoderm, mesoderm, ectoderm)
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What is a carcinosarcoma
Mixed malignant tumours showing characteristics of both epithelium and connective tissue
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Def: oncogenesis
Refers to both benign and malignant tumours
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Def: carcinogens
An environmental agent participating in the causation of tumours. Act on DNA
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Def: carcinogenic
Cancer causing carcinogen
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Def: oncogenic
Tumour/neoplasm causing carcinogen
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Name the classes of carcinogens (7)
1. Chemical
2. Viruses
3. Ionising/non-ionising radiation
4. Hormones
5. Parasites
6. Mycotoxins
7. Miscellaneous
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Characteristics and examples of chemical carcinogens
- No common structural features
- Most require conversion from pro-carcinogens
- Examples: polycyclic hydrocarbons, aromatic amines
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Characteristics and examples of viral carcinogens
- More common in younger people
- Epstein-Barr leads to Burkitt's lymphoma
- Human papillomavirus leads to cervical cancer
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Examples of ionising/non-ionising carcinogens
- UV (UVB more so) exposure gives higher change of basal and squamous cell carcinoma
- Tissues more susceptible to ionising radiation = thyroid, breast, bone, haemopoietic tissue
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Examples of hormonal carcinogens
- Oestrogen increases incidence of mammary and endometrial cancer
- Anabolic steroids increase incidence of hepatocellular carcinoma
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Examples of parasites as carcinogens
- Schistosoma haematobium leads to bladder cancer
| - Clonorchis sinesis results in adenocarcinoma of bile ducts (choleangiocarcinoma)
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Example of mycotoxin as a carcinogen
Alfatoxins produced by Aspergillus flavus -> hepatocellular carcinoma
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2 Examples of asbestos linked tumours
Malignant mesothelioma and lung carcinoma
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5 host factors influencing carcinogenesis
1. Race
2. Diet
3. Constitutional factors (age, gender etc.)
4. Premalignant lesions
5. Transplacental exposure
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How does race influence carcinogenesis
- Skin cancer uncommon in black people - melanin protects from UVB
- Oral cancer more common in India + South-East Asia (chewing tobacco)
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How does diet influence carcinogenesis
- High dietary fat, red/processed meat -> colorectal cancer
- Alcohol -> breast/oesophageal cancer
- Dietary fibre protects against colorectal cancer
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How do constitutional factors influence carcinogenesis
- Inherited presdispostion -> BRCA1/2, RB1 genes
- Age -> incidence increases
- Gender -> breast cancer 200x more likely in women, prostate cancer more common in men
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Premalignant lesions that lead to cancer (5)
- Colonic polyps - bowel cancer
- Cervical dysplasia - cervical cancer
- Ulcerative colitis - bowel cancer
- Undescended testes - testicle tumours
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3 stages of carcinogenesis
Initiation, promotion, progression
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Initiation stage of carcinogenesis
Carcinogen induces genetic alterations that give the cell neoplastic potential
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Promotion stage of carcinogenesis
Stimulation of clonal proliferation of the initiated transformed cell
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Progression stage of carcinogenesis
Culminating in malignant behaviour characterised by invasion and its consequences
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Genetic alterations needed to transform normal cells into neoplastic cells
1. Telomerase expression
2. Loss or inactivation of both copies of tumour suppression gene (removes inhibitory control of cell replication)
3. Activation or normal expression of oncogenes to self stimulate cell proliferation
4. Genomic instability
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Name 2 types of tumour suppressor gene
Caretaker and gatekeeper
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What do caretaker genes do and give an example
Repair DNA damage
| BRCA1/2
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What do gatekeeper genes do and give 2 examples
Inhibit proliferation or promote death of cells with DNA damage
p53
RB1
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Role of p53 gene
- Transcription factor that responds to DNA damage
- Repairs damaged DNA before S phase
- If DNA damage too extensive, initiates apoptotic cell death
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How can p53 lose normal function
- Non sense or missense mutations
- Complexes of normal and mutant p53 that prevent normal function
- Binding of normal p53 to proteins encoded by oncogenic DNA viruses
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Role of RB1
- Transcriptional regulator that controls G1/S checkpoint
| - Associated with retinoblastomas
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5 types of oncogene products
1. Growth factors
2. Receptors for growth factors
3. Signalling mediator with tyrosine kinase activity
4. Signalling mediator with nucleotide binding activity
5. Nuclear-binding transcription factor oncoprotein
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How is an oncogene activated by translocation
Oncogene translocated from untranscribed site to one adjacent to an actively transcribed gene
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How is an oncogene activated by point mutation
Substitution of a single base changes an amino acid resulting in hyperactivity of the oncogene
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How is an oncogene activated by amplification
Insertion of multiple copies of the oncogene resulting in cellular proliferation stimulated by excessive copies
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Factors leading to invasion of tumour
- Decreased cell adhesion to adjacent cells
- Secretion of proteolytic enzymes
- Abnormal or increased cellular motility (more motile and loses contact inhibition mechanism)
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Matrix metalloproteinases
Most important proteinase secreted by malignant neoplastic cells to digest surrounding tissues
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3 major metalloproteinases
1. Interstitial collagenases
2. Gelatinases
3. Stromelysins
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What do interstitial collagenases digest
Collagens I II III
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What do gelatinases digest
Collagen IV and gelatin
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What do stromelysins digest
Collagen IV and proteoglycans
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What inhibits matrix metalloproteinases
Tissue inhibitors of metalloproteinases (TIMPs)
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Tissues with less resistance to tumour invasion
Perineural and vascular lamina
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Tissues with high resistance to tumour invasion
Cartilage and fibrocartilage of intervertebral discs
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Def: Metastasis
The process whereby malignant tumours spread from their site of origin to form other tumours at distant sites
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Def: Carcinomatosis
Extensive metastatic disease
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Which tumour never metastasises
Basal cell carcinoma (cure = excise the whole thing)
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Where does liposarcoma metastasise to
The lung
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Sequence of metastasis
1. Detachment of tumour cells from adjacent cells
2. Invasion of surrounding connective tissue to reach pathway for metastasis (lymphatics/blood vessel)
3. Intravasation into the lumen
4. Evasion of host defence mechanisms (e.g. natural killer cells)
5. Adherence to endothelium
6. Extravasation into surrounding tissue
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Routes of metastasis (3)
1. Haematogenous
2. Lymphatic
3. Transcoelomic
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Metastases in the bone are often from :
1. Lung
2. Breast
3. Thyroid
4. Kidney
5. Prostate
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Describe transcoelomic metastasis
- Pleural, pericardial and peritoneal cavities
| - Effusion contains neoplastic cells -> spread to any organ in cavity
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How do carcinomas most often spread
Lymphatics
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How do sarcomas most often spread
Haematogenous
