Pathology Flashcards
(546 cards)
1
Q
What is acute inflammation?
A
A response of living tissue to injury. Inate, immediate, stereotyped, that acts to limit tissue damage
2
Q
What is the purpose of inflammation?
A
Accumulation of fluid exudate and neutrophils in tissue
3
Q
What can cause acute inflammation?
A
Microbial infections, hypersensitivity reactions, chemicals, necrosis, physica agents (heat, light, radiation)
4
Q
What are the 5 signs of acute inflammation?
A
Redness, swelling, heat, pain and loss of function
5
Q
What are the 3 main tissue level changes that occur in acute inflammation?
A
Change in blood flow, exudate of fluid, infiltration of inflammatory cells.
6
Q
What is the first action that occurs in regards to the change in blood flow in acute inflammation?
A
Transient vasoconstriction (few seconds)
7
Q
After transient vasoconstriction in acute inflammation what 3 things happen? And what signs of inflammation do they account for?
A
Vasodilation of arterioles then capillaries (heat and red), Increased permeability of blood vessels causing exudation and circulation slowing (swelling), increased concentration of RBC in small vessels and increased viscosity- stasis.
8
Q
What causes vascular dilation, transient increase in vascular permeability and pain in acute inflammation?
A
Histamine
9
Q
What releases histamine?
A
Mast cells, basophils and platelets
10
Q
Mast cells, basophils and platelets release histamine in acute inflammation in response to what stimuli?
A
Physical damage, C3a, C5a, IL-1, factors from neutrophils and platelets
11
Q
Histamine accounts for the immediate response in inflammation. What accounts for the persistant response in acute inflammation?
A
Leukotrienes and bradykinin (incompletely understood)
12
Q
What determines fluid flow across vessel walls?
A
Balance of hydrostatic and colloid osmotic pressure
13
Q
What pressures would increase fluid flow out of the vessel?
A
Increase in hydrostatic pressure, increase of colloid osmotic pressure of interstitium
14
Q
In acute inflammation what leads to increase in hydrostatic pressure
A
Arteriolar dilation
15
Q
In acute inflammation what causes an increase in colloid osmotic pressure of the interstitium?
A
Increased permeability of vessel walls leading to loss of protein.
16
Q
Net fluid out of vessels causes what?
A
Oedema
17
Q
What is the difference between a transudate and an exudate?
A
Transudate has the same protein level as plasma. An Exudate has more protein than plasma (inflammation)
18
Q
What is the purpose of oedema?
A
INcreased lymphatic drainage.
19
Q
When do we get a transudate instead of an exudate and why?
A
The fluid loss is due to hydrostatic pressure imbalance only. IN cardiac failure or venous outflow obstruction
20
Q
What are the 5 mechanisms of vascular leakage in acute inflammation?
A
Endothelial contraction-> gaps Cytoskeleton reorganisation-> gaps Direct injury Leukocyte dependent injury Increased transcytosis (through cytoplasm)
21
Q
What chemical mediators are responsible for endothelial contraction in the vascular leakage associated with acute inflammation?
A
Histamine, leukotrines
22
Q
What chemical mediators are responsible for cytoskeleton reorganisation in acute inflammation?
A
Cytokines IL-1 and TNF
23
Q
What chemical mediator induces iucnreased transcytosis in vascular leakage associated with acute inflammation?
A
VEGF
24
Q
What plasma protein in particular is important in exudate formation associated with acute inflammation and why?
A
Fibrin– causes a meshwork localising the products of inflammation. Particulary important in serousal surfaces.
25
What is the primary white blood cell of inflammation and what is another name for it?
Neutrophil- polymorph
26
What is important for the infiltration of neutrophils
Stasis
27
What are the 4 stages of neutrophil infiltration in acute inflammation?/
Margination, Rolling, Adhesion, Emigration
28
What chemicals are important in rolling? And what are important in adhesion?
Selectins for rolling
| Integrins for adhesion
29
How do neutrophils move to the site in acute inflammation?
Chemotaxis- movement along concentration gradient of chemoattractants
30
What are some key Chemotaxins
C5a, LTB5, bacterial peptides
31
What chemical signals facilitate the phagocytic work of neutrophils in acute inflammation?
Opsonins (FC, C3b)
32
The 3 categories of chemical mediators in acute inflammation are
Proteases (kinins, complement, coagulation system)
Prostaglanding/ Leukotrines
Cytokines/Chemokines
33
Proteases (kinins, complement, coagulation system) are found where and produced where?
Produced in the liver and found in the plasma
34
Chemokines in acute inflammation come from where? (TNF, IL-)
WBC
35
```
The primary chemical mediators in acute inflammation for:
Increased blood flow
Vascular permeability
Neutrophil chemotaxis
Phagocytosis
```
Are?
Blood flow- histamines and prostaglandins
Permeability- histamines and leukotrines
Chemotaxis of neutrophils- c5a, LTB4, Bacterial peptides
Phagocytosis- C3b
36
2 hallmark features of acute inflammation are
Exudate of fluid and infilatrate of inflammatory cells
37
How does exudation of fluid combat injury in acute inflammation?
Delivers plasma proteins
Dilutes toxins
Increases lymphatic drainage
38
How does infiltration of cells in acute inflammation combat injury?
Removes pathogenic organisms and necrotic debris
39
How does vasodilation in acute inflammation combat injury?
INcreases delivery and increase temp
40
Why is pain and loss of function important in acute inflammation?
Enforces rest, reduces chance of further damage
41
What are some local complications of acute inflammation?
```
Swelling blocking tubes
Exudate compressing- eg tamponade
Exudate causing serositis
Loss of fluid
Pain and loss of function
```
42
What are some systemic effects of acute inflammation?
Fever
Leukocytes is
Acute phase response
43
What induces a fever in acute inflammation? What is commonly used to treat this
Endogenous pyrogens- Il-1, TBFalpha, prostaglandins
| Aspirin
44
What is leukocytosis and what causes it?
Il-1 and TNF alpha cause accelerated release of macrophages, t lymphocytes from bone marrow.
45
In a reaction to a bacterial infection, induced leukocytosis causes release of what?
What happens in a viral infection?
Bacterial- neutrophils
| Viral- lymphocytes
46
What is the systemic effect of acute phase response in acute inflammation?
Decreased apetite, raised pulse, altered sleep
47
Name some acute phase proteins associated with acute inflammation?
```
CRP
Alpha 1 antitrypsin
Haptoglobin
Fibrinogen
Serum amyloid A protein
```
48
In resolution of acute inflammation what 3 things gradually happen?
Neutrophils no longer migrate
Vessel permeability back to normal
Vessel calibrate returns to normal
49
What needs to be maintained for complete resolution ?
Tissue architecture
50
What happens to the exudate in acute inflammation resolution?
What happens to fibrin?
Exudate drained to lymphatics
| Fibrin degraded by plasmin and proteases.
51
What are some key features of mediators that allows resolution of acute inflammation?
```
Short half lives
Some inactivated by degradation
Some have inhibitors
Some are unstable
Some dilute in exudate.
```
52
Why are skin blisters usually full of clear fluid?
Relatively few inflammatory cells unless bacterial infection
53
What is occurring at the centre of an abscess?
Liquifactive necrosis
54
An effusion is what?
Exudate within a serous cavity
55
What is chronic inflammation?
A chronic response to injury associated with fibrosis
56
What is the most important characteristic in chronic inflammation?
The type of cell present
57
What are the 2 main cells in chronic inflammation?
Macrophages and Lymphocytes
58
What are the functions of lymphocytes?
B lymphocytes to produce antibodies
| T lymphocytes in both control and cytotoxic functions
59
A well as macrophages and lymphocytes what other cells are involved in the chronic inflammatory response?
PLasma cells
Eosinophils
Fibroblasts/myofirbolasts.
60
What does the presence of plasma cells usually imply in chronic inflammation?
Considerable chronicity
61
When are eosinophils present in acute inflammation?
Allergic reactions, parasitic infections and some tumours
62
What is a giant cell?
Multinucleated cell made by fusion of macrophages
63
What are giant cells a result of?
Frustrated phagocytosis
64
What types of giant cells are there? And what are they associated with?
Langhans-> TB
Touton-> fat necrosis
Foreign body type
65
What sort of shape do you commonly see with a langhan giant cell?
Horseshoe
66
What normally surrounds a Touton giant cell
Foamy cytoplasm
67
What is the main difference in the morphology of chronic inflammation compared to acute?
There is a lot more variation in proportions of cells
68
In RA what proportion of cells would you expect to be higher than in other types of chronic inflammation?
Plasma cells
69
What are the 4 main effects of chronic inflammation?
Fibrosis
Impaired function
Atrophy
Stimulation of immune response
70
In chronic cholecystitis what is the cause of the chronic inflammation?
Repeated acute inflammation due to repeated obstruction by gall stones
71
What symptoms would a patient with IBD present with?
diarrhoea, rectal bleeding
72
What is a big difference between ulcerative colitis and crohns?
Ulcerative colitis is superficial (Sx diarrhoea, bleeding)
| Crohns is transmural (Sx strictures, fistulae)
73
Chronic inflammation with fibrosis leads to what?
Cirrhosis (disorganisation of architecture with attempted regeneration)
74
What is granulomatous inflammation
Chronic inflammation with granulomas
75
What is a granuloma
Collection of immune cells (histiocytes)-macrophages stuck together
76
Why would a granuloma form?
The immune system attempts to wall of a substance thought to be foreign but is unable to eliminate it
77
When do granulomas arise?
Persistent low grade antigenic stimulation
| Hypersensitivity
78
What are the 3 main causes of granulomatous inflammation?
Foreign material
Infections (TB)
Unknown (sarcoid, wegeners)
79
How does TB cause disease?
Persistence and induction of cell mediated immunity
80
Why is TB so difficult to destroy?
Wall lipids (mycosides)
81
What is special about a tuberculous granuloma
Caseous necrosis in the centre
82
In cell injury, the degree of an injury depends on what 3 things?
Type of injury
Severity of injury
Type of tissue
83
What is the cell injury response continuum (4)
Homeostasis-> cellular adaption-> cell injury-> cell death
84
7 examples of things that can cause cell injury
```
Hypoxia
Toxins
Physical agents
Radiation
Microorgansims
Immune
Dietary insufficient/ excess
```
85
What is the difference between hypoxia and ischaemia
Hypoxia means decreased oxygen supply, ischaemia is decreased blood supply (worse as its hypoxia and less nutrients, glucose etc)
86
What are 4 typical causes of hypoxia
Hypoxaemic
Anaemic
Ischaemic
Histiocytic
87
What is hypoxaemic hypoxia
Low arterial content of oxygen (could be reduced inspiration, reduced absorbtion)
88
What is anaemic hypoxia?
Low oxygen due to haemoglobins ability to carry oxygen- anaemia or CO
89
What is iscaemic hypoxia
Low oxygen due to interruption of blood supply- blockage or heart failure
90
What is histiocytic hypoxia
The inability of cells to utilise oxygen due to disable oxidative phosphorlyayion enzymes (Cyanide)
91
Typically how can the immune system damage its own cells?
```
Hypersensitivity reactions
Autoimmune reactions (not recognising self)
```
92
What components of the cell are most succeptible to injury
Cell membranes (plasma and organelle)
Nucleus (DNA)
Proteins (enzymes)
Mitochondria
93
What is the first outcome of hypoxia on a cell in a reversible injury?
Decreased oxidative phosphorylation
94
In a reversible cell injury, there is the initial decrease in oxidative phosphorylation. What is the result of this?
What 3 changes does this induce?
Decreased ATP
Decreased activity of the Na/K pump
Increased glycolysis
Detachment of ribosomes, decreasing protein synthesis
95
Due to decreased ATP in a reversible injury to the cell the Na/K pump isn't working well. What is the resultant electrolyte change and what changes can be seen?
Influx of calcium, H2O and Na+. Efflux of K+
Cellular swelling, blebbing, ER swelling, myelin figures
96
Due to a decrease in ATP in a reversible hypoxic injury there is a increase in glycolysis.
What is the effect of this
Decreased PH, decreased glycogen.
| Clumping of nuclear chromatin (due to ph Change)
97
IN a reversible hypoxic injury there is decreased ATP production leading to less protein synthesis.
How is this seen in the cell?
Lipid deposition
98
In prolonged, irreversible hypoxia what is the main agent that accumulates in the cytosol?
Calcium
99
INcreased cytosolic calcium in prolonged hypoxia induces what 5 things? Leading to what?
ATPase->decreased ATP
Phospholipase->decreased phospholipids
Protease-> disrupts membranes and cytoskeletons
Endonuclease-> chromatin damage
100
What primarily damages membranes in hypoxia?
Free radicals
101
What is a free radical?
reactive oxygen species with single unpaired electron
102
3 free radicals of particular biological importance?
Hydroxyl OH
Superoxide O2-
Hydrogen peroxide H2O2
103
What are the 2 physiological mechanisms in which free radicals are produced?
In metabolic reactions like oxidative phosphorlyation
| In inflammation- oxidative burst of neutrophils
104
What 3 pathological mechanisms induce free radical production?
Contact with unbound metals- iron, copper
Radiation
Drugs and chemicals
105
What 3 mechanisms does the body have to control free radicals?
Anti-oxidant system
Metal carrier and storage proteins
Enzymes that neutralise free radicals
106
What are the anti-oxidant vitamins and how do they work?
A,C,E
| Donate electrons
107
What are some examples of metal carriers that sequester iron and copper?
transferrin, ceruloplasmin
108
What enzymes are responsible for neutralising free radicals
superoxide dismutase
Catalase
Glutathione peroidase
109
What is oxidative imbalance?
The number of free radicals overwhelming the anti-oxidant system
110
What are the most important targets of free radicals in the cell? And what do they cause
Lipids- lipid peroxidation
111
What is an autocatalytic chain reaction in relation to lipid peroxidation
The generation of further free radicals
112
Other than lipid peroxidation what effect can free radicals have on the cell
Oxidise proteins, carbohydrates and dna
| Beings out of shape or cross linking.
113
How can the cell protect itself from injury?
Heat shock proteins
114
What is the role of a heat shock protein?
Aim to mend misfiled do proteins and maintain cell viability
115
Heat shock proteins are (2) e.g
Unfoldases
Chaperonins
Eg ubiquitin
116
What does an injured cell look like under a microscope
Bit pale and swollen (movement in of sodium and water)
117
What does a dead cell look like under microscope?
Very pink cytoplasm (denature and coagulation)
| Nucleus changes
118
What 3 changes in the mucleus can be seen in dead cells
Pyknosis
Karyorrhexis
Karyloysis
119
Under an electron microscope what can be seen in the cell in a state of reversible injury?
( can already see general swelling and pale staining under microscope)
```
Blebs
Clumping of chromatin
ER swelling
Dispersion of ribosomes
Mitochondrial swelling
```
120
Under electron microscope of a dead cell, what additional features can we see compared to the microscope?
(Already seen change in nucleus (pyknnosis, karyohexis or karyolysis) and increased staining
Rupture of lysosomes, cell membrane defects, lysis of ER, myelin figures
121
How do we diagnose cell death?
INjection of dye- dead cells cant keep it out
122
What is necrosis
Morphological changes that occur after a cell is dead
123
What is oncosis
Cell death with swelling, the spectrum of changes prior to death
124
What are the 2 main types of necrosis and the 2 special types
Main: coagulative, liquifactive
Special: Caseous, fat
125
Where does coagulative necrosis occur?
Ischemia in solid tissues
126
What process dominates in coagulative necrosis?
Protein desaturation
127
Where does liquifactive necrosis occur and what is there a prescence of?
Loose tissue
| Neutrophils
128
What predominated in liquifactive necrosis?
Enzyme release
129
What does coagulative necrosis look like?
Cellular architecture preserved
Darker staining
Protein desaturation> proteases
130
What does liquefactive necrosis look like?
Loss of cell architecture
| Essentially dissolved away
131
What does caseous necrosis contain ?
Structureless debris
132
What is caseous necrosis associated with?
TB
133
What does fat necrosis look like? What causes it
Large fat drops surrounded by macrophages
| Leaking of lipid that combine with calcium to form calcium soaps.
134
What is gangrene
Necrosis visible to the naked ete
135
What is an infarction
Necrosis caused by reduction of arterial blood flow
136
What is an infarct
An area of ischaemic necrosis
137
What is dry gangrene?
Necrosis modified by exposure to air (coagulative)
138
What is wet gangrene?
Necrosis modified by infection (liquifactive)
139
What are the commonest causes of infarction?
Thrombosis
| Embolism
140
Why are some infarcts white?
Occlusion of end artery. Coagulative necrosis. Often wedge shaped
141
Why are some infants red?
Loose tissue
Dual blood supply
Raised venous pressure
Re-perfusion
142
What is ischaemia-reperfusion injury?
Paradoix- blood flow returned to damaged but not yet necrotic tissue inducing more damage
143
3 important things that leak out in cell death-
Potassium
Enzymes
Myoglobin
144
Why is the release of K in cell death dangerous
Hyperkalemia leading to cardiac arrest
145
If myoglobin leaks out, what can be a clinical sign?
Rhabdo
146
What is the biggest macroscopic difference in the cell undergoing apoptosis compared to necrosis
The cell shrinks rather than swells
147
Is apoptosis an active or passive process?
Active
148
What happens to the membrane in apoptosis?
Membrane integrity is maintained
149
are lysosomal enzyme involved in apoptosis?
NO
150
Is apoptosis pathological or physiological?
Both
151
What happens to dna and proteins in apoptosis
Enzymes degrade them
152
When does pathological apoptosis occur?
Cytotoxic T cells killing virus/neoplastic cell
Damaged cell (particulary dna)
Graft v host
153
3 stages of apoptosis
Initiation (Condensation), execution (fragmentation),degradation and phagocytosis (apoptic bodies)
154
What 2 mechanisms trigger initiation and execution of apoptosis?
Intrinsic and extrinsic
155
The intrinsic and extrinsic activation of apoptosis result in what?
Activation of caspases
156
What is the role of caspases?
Control and mediate apoptosis
| Cause cleavage of dna and proteins
157
What are the most common triggers for the intrinsic pathway?
Irreparable dna damage, withdrawal of growth factors
158
What do the triggers in the intrinsic pathway of apoptosis activate? And what's its effect?
P53, makes mitochondrial membrane leaky
159
What is released from a leaky mitochondrial membrane in apoptosis? And what does it do?
Cytochrome C- causes activation of caspases
160
What is the trigger to the extrinsic pathway of apoptosis? An example of a signal?
Cells that are a danger- tumour, virus
| TNF alpha
161
What does TNF alpha, secreted by a T killer cell do to induce apoptosis?
Bind to death receptor, resulting in activation of caspases
162
How are apoptotic bodies phagocytosed
Express proteins on surface recognised by phagocytes
163
What are the 5 main groups of intracellular accumulation?
```
Water and electrolytes
Lipids
Carbohydrates
Proteins
Pigments
```
164
What does fluid accumulation in cells indicate? Where is this a particular problem
Cellular distress. Na+ and water into cell.
| The brain
165
What is steatosis?
Accumulation of triglycerides
166
Where is lipid accumulation often seen?
Liver. (Major organ of fat metabolism)
167
What can cause fatty liver?
Alcohol
Diabetes
Obesity
168
Why does cholesterol accumulate in cells in vesicles?
Insoluble, eliminated only though the liver
169
Where does cholesterol accumulate if in excess?
Smooth muscle cells and macrophages in plaques (foam cells). Macrophages in skin and tendons- xanthomas
170
How are protein accumulations seen?
Eosinophilic droplets in cytoplasm
171
What conditions can result in protein accumulation in cells?
Alcoholic liver disease
| Alpha 1 antitrypsin deficency.
172
What are examples of pigment accumulations?
Carbon
Coal
Dust
Soot
173
Why do pigment accumulations occur?
Phagocytosis by macrophages
174
What is an example of an endogenous pigment accumulation?
Haemosiderin in a bruise
175
What is haemosiderin?
Iron storage molecule derived from haemoglobin
176
In haemochromatosis where is iron deposited and what is it often associated with?
Skin, liver, pancreas, heart
| Scarring
177
What are 4 mechanisms of intracellular accumualtion?
Abnormal metabolism
Alteration in protein folding and transport
Deficency in critical enzyme
Inability to phagocytosis particles
178
What is dystrophic calcium deposition
deposition of calcium salts in an area of dying tissue
| Plaques, heart valves, lymph nodes
179
Is dystrophic calcification associated with abnormality in calcium metabolism or calcium concentrations in serum?
NO
180
Why does dystrophic calcification occur?
Local change that favours nucleation of hydroxyapatite crystals
181
Why does metastatic calcification occur?
Due to hypercalcaemia secondary to disturbance in calcium metabolism
182
What 2 things cause hypercalcaemia?
Increased secretion of parathyroid hormone
| Destruction of bone tissue
183
What is disease characterised as?
Pathological condition of a body part, organ or system characterised by identifiable group of signs and symptoms
184
What is pathology?
Understanding the process of disease and why you have symptoms
185
What is cytopatholoy?
Looking at diaggregated cells rather than tissues
186
What is the purpose of microscopic diagnosis?
Aid in definitive diagnosis and guide extent of intervention
187
What's the difference between cytology and histology?
Cytology is the cellular level, histology is the architecture of the tissue
188
What are some clinical examples of histology?
Core biopsies, cancer resection, endoscopic biopsies
189
What are some examples of clinical cytology
Fine needle aspirates- breast, thyroid, lung, sputum, urine, cervical smear
190
What is more invasive typically cytology or histology?
Histology
191
What is generally cheaper cytology or histology?
Cytology
192
What is an issue with cytology?
Generally has higher error rates
193
What is a major advantage of cytology
Fast and cheap
194
What is the cancer staging mnemonic
TNM
195
What does TNM stand for in cancer staging
Tumour, Nodes, Metastisis
196
What would be the worst cancer staging?
T3N2M(high number)
197
What is the first thing that needs to be stopped when preparing a slide for histology?
Autolysis
198
What is autolysis when preparing a slide?
Self digestion (begins to occur once blood supply lost)
199
How is autolysis inhibited in slide preparation?
With use of fixatives
200
What do fixatives do, in refereance to slide preperation
Inactivate tissue enzymes and denature proteins, present bacterial growth and harden tissue
201
What is the normal fixative used in slide preparation?
Formalin
202
What is trimming?
Slicing of a specimen into stamp size pieces to be put in a cassette
203
What happens after trimming in slide preparation?
Water is removed from the tissue
204
How is water removed from tissue in slide preparation?
Alcohol
205
How is alcohol removed from a slide (added to remove water)
use of xylene
206
What is paraffin wax used for in slide preparation? When is it added?
Embedding
| After xylene has been added
207
What happens once a tissue has been embedded in paraffin wax in slide preparation?
Blocking- placed on freezing surface.
208
The slide is now embedded and has been blocked. What happens now before the slide is stained?
Cut with microtome. Water bath to remove wrinkles
209
What is the normal tissue stain, what does it stain
H (nuclei purple)
| E (cytoplasm pink)
210
What is immunohistochemistry?
Labelling with specific antibodies to demonstrate a substance is present
211
In immunohistochemistry an antibody is normally joined to what? Why?
Peroxidase enzyme- catalyses colour change
212
How are things like her2, cadherins, actin demonstrated in a tissue slide?
Immunohistochemistry
213
What is the use of cytokeratins in cancer diagnosis?
Can indicate primary site (difference cytokeratins)
214
What cytokeratins are form the lung, breast, endometrium, ovary or thyroid?
CK7+ / CK20-
215
What cytokeratins are from the large bowel
CK7- / Ck20+
216
What can molecular pathology use FISH for?
Look at amount of gene copies (aids in treatment choice)
217
In molecular pathology what is more useful to look at than the gene or amount of gene copies when using it to guide treatment? Why?
MRNA expression. Better shows what gene is being transcribed
218
What is a tumour signature?
The mRNA expression from the tumour. Aids in prediction of its behaviour
219
To what accuracy does a frozen section have?
96%
220
Why do we still use post mortems given the advent of modern imagining and biochemistry?
Discrepancies still in modern imaging
221
When does an autopsy not require consent?
When its on behalf of HM cornonor
222
What are some examples of reasons to have a HM coroner autopsy?
If deceased unknown
Deceased not seen by a doctor within 14 days of death
Attending doctor cant give cause of death
Unnatural death
Relation to occupational disease or accident
Related to medical treatment
Forensic
223
When is consent required for an autopsy?
In hospital autopsies that aren't on Hm coronoers orders
224
What occurs in an autopsy?
```
External exam and internal looking at all systems
Histology
Toxicology
Biochemistry
Microbiology
Molecular dna based ax
```
225
Who can perform a paediatric autopsy?
Someone trained in paediatric surgical pathology and autopsy
226
What would a paediatric pathologist look at in autopsy (type)
In utero, perinatal, death in infants and children that are suspicious
227
A hit on the head leading to a 'slow leak' is likely what kind of haemorrhage
Extradural
228
What kind of haemorrhage is a berry aneurysm
Sub-arachnoid
229
What are the two types of stroke?
Ischaemic and haemorrhagic
230
What types of intracranial haemorrhage are there?
Extramural, subdural, subarachnoid, intracerebral
231
What happens in diffuse atonal injury
Axons are broken
232
What can raised ICP cause
Resp and cardiac issues.
| Decreased consciousness
233
What happens in a tension pneumothorax
Air is within the pleural cavity, when the lung expands more air moves into pleural cavity
234
When is hypovolemia life threatening
20% blood volume
235
What are some systemic effects of burns?
Increased vascular permeability
Reduced myocardial contractility and end organ hypoperfusion
Non specific down regulation of the immune system
236
What are some clinical features of sepsis?
```
Mottled skin
Cap refill less than 3
Decreased urine output
Lactate above 2 mol
Cardiac dysfunction
Change in mental state
Platelets above 100
Troponin leak
ARDS
DIC
```
237
What is ARDS
Acute resp distress syndrome
| Neutrophil sequestration and migration into alveolus causing oedema and necrosis of type 1 cells
238
What are the 3 basic processes involved in wound healing? And why?
Haemostasis - the vessels are open
Inflammation- there is tissue injury
Regeneration- structures have been injured or destroyed
239
Regeneration in wound healing can be either what?
Resolution of restitution
240
What is healing by primary intention
Restitution with no or minimal evidence of previous injury
241
When does healing by primary intention occur?
Superficial abrasion
242
Generally on a skin level what is the difference between an abrasion and an ulceration?
Abrasion the top few layers of skin
| Ulceration is something deeper
243
In the gut what specifically is the difference between an abrasion and an ulceration?
An ulceration penetrates the muscularis layer
244
What cells replicate in regeneration
Stem cells
245
What 3 things do stem cells display?
Prolonged proliferative activity
Asymmetric replication
Internal repair system
246
Where are stem cells located in the epidermis?
Basal layer adjacent to basement membrane
247
Where are stem cells located in the intestinal mucosa?
Bottom of crypts
248
Where are stem cells located in the liver?
Between hepatocytes and bile ducts
249
What are most adult stem cells?
Unipotent
250
What does being a unipotent stem cell entail?
Able to produce one type of differentiated cell
251
What is a multipotent stem cell? And an example?
Produces several types of differentiated cell
| Haematopoeitc stem cell
252
An embryonic stem cell is what type of stem cell
Totipotent
253
What can a totipotent stem cell do?
Produce any type of cell and therefore any type of tissue
254
What tissues cant undergo mitosis and have no or few stem cells?
Permanent tissues
255
What are some examples of permanent tissues
Skeletal muscle
Neural tissue
Cardiac muscle
256
What tissues contain short lived cells?
Labile tissues
257
What are some examples of labile tissues?
Surface epithelial, haematopoeitc tissues
258
What tissues have low levels of replication but can undergo rapid proliferation of needed?
Stable tissues
259
What are some examples of stable tissues?
Liver parenchyma, bone, fibrous tisssue, endothelium
260
What are the 3 tissue type (labile, stable and permanent) divided based upon?
Proliferation activity (based on cell cycle)
261
What 3 circumstances are needed for regeneration to occur
The tissue is label/ stable
The tissue damage is not extensive
Intact connective tissue scaffold
262
What is fibrous repair?
Healing with formation of fibrous connective tissue (Scar)
263
What tissue is often lost for fibrous repair to occur
Specialised tissue
264
When does fibrous repair occur?
Significant tissue loss
| Permanent or complex tissue is injured
265
What is the first stage in scar formation? What time frame?
Haemostasis
| Seconds-minutes
266
What is the second stage in scar formation? What time frame
Acute inflammation
| Minutes to hours
267
What is the third stage in scar formation? What time frame
Chronic inflammation
| 1-2 days
268
What's the fourth stage in scar formation? After chronic inflammation, and roughly when does that begin
Granulation tissue forming at 3 days
269
When does early scar fomration take place ?
7-10 days
270
Over what time period does scar maturation occur?
Weeks- 2 years
271
What does granulation tissue consist of?
Developing capillaries
Fibroblasts and myofibroblasts
Chronic inflammatory cells
272
What is the function of granulation tissue?
Fills the gap
Capillaries bring oxygen and nutrients
Contracts and closes gap
273
In fibrous repair a blood clot initially forms. What cells follow this?
Neutrophils to digest clot
| Macropages and lymphocytes
274
In fibrous repair what is synthesised from the vascular network?
Collagen
275
What does the collagen do once deposited in fibrous repair
Matures, contracts and remodels
276
What are the 3 cell/ cell groups involved in fibrous repair
Inflammatory cells
Endothelial cells
Fibroblasts/myofibroblasts
277
What is the role of inflammatory cells in fibrous repair?
Phagocytosis Debi's and produce chemical mediators
278
What is the purpose of the endothelial cells in fibrous repair
Angiogenesis
279
Fibroblasts and myofibroblasts do what in fibrous repair?
Produce extracellular matrix
| Responsible for wound contraction
280
Why are scars white?
No regeneration of melanocytes
281
What do scars tend to stretch?
We dont lay down elastin with them
282
What can tends to be absent on scar tissue ?
Sweat glands and hair follicles
283
Why is a scar initially red?
Lots of blood vessels present
284
What are amorphous collagens and what are they for?
Collagens 4-9 things like basement membrane
285
What collagen is most common and where's it found?
Type 1- bones, ligaments, skin, blood vessels
286
What collagen makes up basement membranes
Type 4
287
What are some symptoms of scurvy
Unable to heal wounds
Tooth loss
Old scars break open
288
What do the collagen fibres in Ehlers danlos lack?
Tensile strength
289
What change in the eye is seen with osteogenesis imperfecta?
Blue sclerae- too little collagen within them
290
What is abnormal in Alport syndrome
Type 4 collagen
291
What are growth factors?
Polypeptides that act on cell surface receptors
292
What are growth factors coded by/
Porto-oncogenes
293
What do growth factors stimulate?
Transcription of genes that regulate entry of cell into cell cycle
294
Other than cell proliferation what effects can growth factors have?
```
Inhibition of division
Locomotion
Contractility
Differentiation
Viability
Angiogenesis
```
295
Name 4 growth factors
Tumour necrosis factor
Platelet derived growth factor
Vascular endothelial growth factor
Epidermal growth factor
296
What do cadherins do?
Bind cells to each other
297
What do integrins do?
Bind cells to extracellular matrix
298
What does contact inhibition do?
Inhibits proliferation in intact cells, encourages it in damaged cells
299
When can contact inhibition be altered?
Malignant cells
300
What is healing by primary intention?
Incision, closed, non-infected and sutured wounds.
Small number of disrupted cells
Minimal clot and granulation tissue
301
What is healing by secondary intentions?
Excisional wound with tissue loss and seperated edges.
| Filled by abundant granulation tissue, grows in from wound margins
302
In secondary intention healing the new epdidermis is often what?
Thinner than usual
303
Skin grafts are taken at what thickness?
Split thickness
304
What are some general factors that influence wound healing?
```
Age
Obesity
Diabetes
Vitamin deficiencies and malnutrition
Anaemia, hypoxia, hypovolaemia
Drugs
```
305
What can occur if there is insufficient fibrosis (scarring) in fibrous repair?
Wound dehiscence, hernia, ulceration
306
What are some complications of fibrous repair
```
Adhesion formation
Loss of function (replacement of specialised tissue)
Disruption of complex tissue
Overproduction of scar
Excessive contraction of scar
```
307
What is the general purpose of haemostasis
To prevent bleeding
To prevent unesscesary coagulation
To allow blood flow
308
What is haemostasis the process of ?
Making a clot, controlling the clotting and breaking the clot down
309
What are the 3 stages of the clotting process
Initiation
Formation
Fibrinolysis
310
In clot initiation what is happening? Re platelets
Platelet aggregation to vessel wall and activation of coagulation
311
In clot formation once the platelets have aggregated against the vessel wall what is the key conversion that occurs in the activation of the coagulation pathway?
Thrombin converts fibrinogen to fibrin which forms fibrin polymers
312
In fibrinolysis what is occurring generally?
Retraction of fibrin polymers and breakdown of fibrin fragments
313
How do platelets look on a H and E
Non nucleated purple staining dots
314
What produces platelets
Megakaryocytes (bud off from cytoplasm)
315
What is the normal platelet range
150-400 x 10^9
316
What is the normal lifespan of platelets
7-10 days
317
What drug is an antiplatelet?
Aspirin
318
When damage to vessel walls occurs what encourages platelet adhesion? Via what receptor?
Exposed collagen
| VWF receptor
319
What activated other platelets once platelet adhesion has occurred?
Secretion of ADP and thromboxane
320
What do the platelets do once they have aggregated against a damaged vessel wall
Cross link to form platelet plug
321
What is the platelet plug mediated by?
Von willebrands factor, fibrinogen, collagen, thromboxane and thrombin
322
How does the clotting process itself limit clotting?
Negative feedback loop where the clot destroys proteins activated by the clotting cascade
323
What do we have naturally occurring the inhibit the activation of the clotting cascade?
Natural anticoagulants
324
Both coagulation factors and natural anticoagulants are made where?
Liver
325
What 2 clotting pathways are there? Where do they converge?
Intrinsic and extrinsic
| X
326
Which clotting pathway involves factor
Extrinsic (PT)
327
Which clotting pathway involves factors 8,9,11,12?
Intrinsic/ APPT
328
What clotting factors do both the intrinsic and extrinsic involve?
V, X, prothrombin, fibrinogen
329
What is APTT a measure of?
The intrinsic pathway
330
What is PT a measure of?
The extrinsic pathway
331
In clotting tissue factor exposure activates what ?
FVII
332
When the activation of FVII occurs and thrombin is made. What happens to massively amplify the process?
Thrombin burst. (Lots of clotting factors and thrombin)
| Thrombin feeding back in the cascade
333
What is Von willebrands factor involved in?
Platelet adhesion to vessel wall. Platelet aggregation
| Carries factor VIII
334
What is activated in fibrinolysis to breakdown fibrin mesh?
Plasminogen activated to plasmin
335
What does plasmin breakdown? To what?
Fibrin to D dimers
336
What are some natural anticoagulants?
Protein C
Protein S
Antithrombin
337
Deficency in protein c, protein s or anti thrombin results in what?
Thrombophillia
338
Are bleeding disorders inherited or acquired?
Both
339
Where can abnormalities be to lead to a bleeding disorder?
Vessel wall
Platelets
Coagulation factors
340
Haemophilia A is a disorder of what?
Clotting factor 8
341
Haemophilia B is a disorder of what
Clotting factor 9
342
What acquired disorders can lead to clotting disorders?
Liver disease
Vitamin k deficency (needed for 2,9,10,7)
A
343
What symptoms would a coagulation factor disorder present with?
Muscle haematomas
Recurrent haemarthroses
Joint pain and deformity
Excessive post surgical bleeding
344
Haemophilia A has what generic pattern
X linked recessive
345
How is haemophilia A treated
Recombinant factor 8
346
Someone presents with skin and mucous membrane bleeding. But doesn't report haemartroses or muscle haematoma.
What would you think it is?
Von willebrands disease
347
What occurs in Von willebrands disease?
Abnormal platelet adhesion and reduced factor 7 activity
348
What symptoms are associated with a vessel wall abnormality (haemostasis)
Easy bruising, spontaneous small bleeds. Mainly skin but also mucous membrane
349
Name a congential disease associated with vessel wall abnormality
Hereditary haemorrhagic telangiectasia
350
What are some acquired diseases of the vessel wall?
Senile purpura
Meningococcal
Measles
351
Platelet disorders can either be what?
Qualitative or quantitative
352
A quantitative disorder of the platelets is known as
Thrombocytopenia
353
What can a low platelet count be a result of generally
Reduced production or increased removal
354
The increased removal of platelets inducing thrombocytopenia could be due to what?
Immune destruction
Non immune destruction
Splenic pooling
355
If the production of platelets is low what should you look at?
Bone arrow and the megakaryocytes
356
What is an example of immaterial destruction of platelets?
Immune thrombocytopenia purpura
357
In Immune thrombocytopenia purpura what is happening? What can it be secondary to?
Antibodies against glycoproteins on platelet surface are produces.
Secondary yo disease like lupus or lymphoma
358
How would you treat Immune thrombocytopenia purpura
Immune supression
359
What is an example of non immune destruction of of platelets?
Microangiopathic haemolytic states like DIC
360
What thrombocytopenias are due to low production of platelets?
B 12 defficency
Bone marrow cancer
Chemo
HIV
361
What could happen if platelet count falls below 30?
Mucousal bleeding
| Intracranial haemorrhage
362
What is more common an acquired platelet function disorder or hereditary
Acquired
363
What are some common examples of acquired platelets function disorder causes
Aspirin
NSAIDS
Uraemia
Myeloproliferative disorder
364
What is DIC an example of
Microangiopathic haemolytic anaemia
365
What are formed in DIC
Microthrombi
366
Why are microthrombi formed in DIC
Pathological activation of coagulation
367
In DIC what would clotting tests show and why?
Increased clotting times as clotting factors and platelets are used up
Raised d dimers from breakdown of clots
368
Is DIC a diagnosis?
No there is always a trigger
| Malignancy, infection, obstetric cause etc
369
What is atheroscelerosis an accumulation of?
Intracellular and extracellular lipid
370
Where does atherosclerosis occur?
Intima and media of medium to large arteries
371
What is the result of atherosclerosis?
Thickening and hardening of the walls of arteries
372
What is the time line of atherosclerosis?
Fatty streak-> simple plaque-> complicated plaque
373
What is the macroscopic appearance of the fatty streak in atherosclerosis formation?
Lipid deposits in intima, yellow and slightly raised
374
What's the macroscopic appearance of the simple plaque in atherosclerosis?
Raised yellow/white with irregular outline and wide distribution
375
What is the complicated plaque in atherosclerosis?
Thrombosis followed by haemorrhage into plaque, calcification and the formation of an aneurysm
376
Where are some common sites of atherosclerosis?
Aorta (especially abdominal), coronary arteries, carotid arteries, cerebral arteries, arteries of the leg.
377
What is the normal structure of an artery (out to in)
Endothelium, internal elastic lamina, muscularis media, external elastic lamina, adventitia
378
What are some early microscopic features of atherosclerosis?
Smooth muscle proliferation
Accumulation of foam cells
Extracellular lipid
379
What are some mid stage- late changes in atherosclerosis microscopically?
Fibrosis
Necrosis
Cholesterol clefts
Occasional inflammatory cells
380
What are the late stages of atherosclerosis as seen microscopically
Disruption of internal elastic lamina
Damage into media
Ingrowth of blood vessels
Plaque fissuring
381
What are some clinical consequences to atherosclerosis of coronary arteries?
Ischaemic heart disease-
| MI, Angina pectoris, Arrythmias, Cardiac failure
382
What does a myocardial infarction look like macroscopically
Yellow with red border, known as hyperaemic border
383
What are some clinical effects of cerebral atherosclerosis
Cerebral ischemia leading to
TIA
Cerebral infarct
Multi-infarct dementia
384
How are cerebral infarcts seen macroscopically
Small area of infarct and a large area of haemorrhage
385
What would the clincal effect of mesenteric ischaemic manifest itself as?
Ischaemic colitis, malabsorption, intestinal infarction
386
What can peripheral vascular disease lead to?
Intermittent claudication
Leriche syndrome (buttocks and impotence)
Ischaemic rest pain
Gangrene
387
What are some risk factors for atherosclerosis?
```
Age
Gender (women protected before menopause)
Hyprelipidemia
Cigarette smoke
HTN
DM
Alcohol
Infection
```
388
Why is the initial endothelial injury taking place in atherosclerosis?
Raised LDL
Toxins
HTN
Haemodynamic stress
389
What is the first thing to happen in atherosclerosis development?
Endothelial injury
390
After endothelial injury in atherosclerosis what happens re platelets?
Platelet adhesion
Platelet derived growth factor release
Smooth muscle proliferation and migration
391
After endothelial injury in atherosclerosis what happens re lipids?
Insudation of lipid
LDL oxidation
Uptake of lipid by smooth muscle cell and macrophage
392
After endothelial injury in atherosclerosis what happens re monocytes
Migrate to intima
393
In atherosclerosis, once endothelial damage has occurred. The platelets have adhered, the lipid has insudated and the monocytes have migrated, what do smooth muscle and foam cells do?
SMC produce matrix material
| Foam cells secrete cytokines that cause further SMC stimulation and recruit inflammatory cells
394
What's a thrombosis?
Solid mass of blood within circulatory system during life
395
What's the difference between a clot and a thrombosis
Clot occurs at skin level/ test tube/ breakage of the continuity of vessel
396
What causes thrombosis
Wircoffs triad
Abnormalities in vessel wall
Abnormalities in blood flow
Abnormalities in blood components
397
What are some vessel abnormalities that might lead to a thrombosis
Atheroma (plaque)
Direct injury (not a cut)
Inflammation (like in vasculitis)
398
What kin of abnormalities in blood flow might cause a thrombus
Stagnation (eg DVT)
| Turbulence (eg aortic stenosis)
399
What kind of abnormalities in blood components can assist in causing a thrombosis
Post partum
Post op
Smoking
400
What is the macroscopic appearance of a thrombis in an artery?
Pale, granular with lines of zahn, a lower cell contents
401
What creates the lines of zahn seen in a thrombosis in the arteries?
At times there are less red cells being laid down making it appear paler.
402
Macroscopically how would a thrombus appear in a vein?
Soft, gelatinous, deep red with a high cell content
403
What are 5 potential outcomes of thrombosis ?
```
Lysis
Propogation
Organisation
Recanalisation
Embolism
```
404
What is lysis in reference to a thrombosis
The complete dissolution of thrombus thanks to the fibrolytic system, bloodflow re-established
405
What is organisation in reference to a thrombosis?
Reparative process
Ingrowth of fibroblasts and capillaries much like granulation tissue
Lumen remains obstructed
406
What does the tissue of an organised thrombus resemble?
Granulation tissue
407
What is propogation in relation to thrombosis? What direction would this travel
Progressive spread of thrombosis
Dismally in arteries
Proximal in veins
408
What is recanalisation in reference to thrombosis
Blood flow is re-established but is usually incompetent
| One or more channels form through organising thrombus
409
What is thrombo-embolism?
Part of thrombus breaks off, travels through blood stream lodging at distant site
410
Where do arterial and venous thrombo-embolisms travel
Veins back towards the heart.(usually ending in the lungs)
| Arteries away from the heart (commonly renal and mesenteric)
411
What does an arterial thromboembolism usually result in (that a venous one is less likely to)
Ischaemia, infarction
412
When will an infarction not develop from an arterial embolism?
If there is collateral circulation sufficient enough to not allow ischamia to take place
413
What is a venous embolism likely result in? When may this develop to ischaemia and infarction?
Usually congestion and oedema due to increased hydrostatic pressure.
Ischaemia and infarction develop if pressure reaches the same as the arterial side.
414
What is an embolism?
Blockage of blood vessel by solid, liquid, gas from distant site of origin (90% thrombo embolism) next most common is air
415
How much air is needed to induce an air embolism? What does it do to blood
150ml
| Makes blood froffy and hard to pump
416
Where would the fat in a fat embolism be released from?
Bone marrow typically
417
What are the 3 determinants of cell population ?
Rate of proliferation
Rate of differentiation
Rate of apoptosis
418
Cell proliferation can be pysiological or pathological, what is prostatic hypertrophy an example of?
Physiological developing into pathological
419
What regulated normal cell proliferation?
Porto-onco genes
420
What controls cell proliferation, altering the expression of proto-onco genes
Chemical signals from the micro-environment
421
How does a chemical signal alter the expression of proto-oncogenes
Singalling molecule eg steroid, binding to a receptor, usually located in cell membranes in cytoplasm or nucleus and then either activation or inhibition of a genes expression
422
What are the basic 4 things a chemical signal can tell a cell to do re cell growth
Survive
Die (apoptosis)
Divide
Differentiate
423
To increase the cell population, what 2 options are available?
Shorten cell cycle
| Recruit quiescent cells back into cell cycle
424
What can looking for mitosis tell us about a cancer?
Aid to grade how aggressively they are dividing
425
In the normal cell, what stops it replicating with damaged dna?
Cell cycle checkpoints
426
What is the most critical cell cycle checkpoint?
The R point
427
Why is the R point the most critical cell checkpoint?
The majority of cells that pass the R point will complete cell cycle
No external signals are needed
428
Before the R point, what signals is the cell responsive to?
Mitogenic growth factors
| TGF-beta
429
What is the most commonly altered checkpointt in cancers?
R point
430
At the R point what can delay the cell cycle, activate repair mechanisms or apoptosis
P53
431
What molecules internally control the cell cycle
Cyclin and cycli dependent kinases
432
How do cyclins and cyclin dependent kinases work?
Cyclin binds to the substrate (target protein), Cyclin dependent kinase phosphorylates it to give the desired action
433
What is the Leonard hayflick number
The number of times cells can divide
| 61
434
What is hyperplasia
Increase in cell number
435
What tissues does hyperplasia occur in
Labile and stable tissue
436
Why does physiological hyperplasia occur
Increased functional demand or hormone stimulation
437
What's the difference between physiological and pathological hyperplasia
Physiological is reversible as it is under control
438
What does pathological hyperplasia increase the risk of?
Mutations
439
What's an example of physiological hyperplasia and pathological hyperplasia
Bone marrow response in hypoxia at altitude
| Goitre in iron defficency
440
What is hypertrophy
Increase in cell size
441
What tissues does hypertrophy occur in?
Labile, stable and permanent (especially)
442
Why does hypertrophy occur?
Increased demand or hormonal stimulation inducing more cell structural component
443
What is hypertrophy usually accompanied by in labile and stable tissues
Hyperplasia
444
What's compensatory hypertrophy
Another organ becoming enlarged as the result of poor function elsewhere
445
What's an example of pathological and physiological hypertrophy
Phys- gainz
| Path- hypertrophy in HTN of cardiac muscle
446
What is atrophy
Decrease in size and or number of cells
447
What is tissue atrophy often a combination of?
Cellular atrophy and apoptosis
448
What happens at a cellular level in atrophy
Autophagosomes get rid of cellular components it doesnt need- forming residual bodies
449
What is an example of physiological atrophy
Ovarian atrophy post menopause
450
What is metaplasia?
Reversible change of cell type
451
What is metaplasia due to?
Altered stem cell differentiation
| Adaptive substitution of cells sensitive to stress
452
What is metaplasia often a prelude to?
Dysplasia and cancer
453
What tissues can undergo metaplasia
Labile and stable
454
What does metaplasia not occur across?
Germ layers
455
What are examples of metaplasia?
Change in bronchial pseudostratified to stratified squamous in cigarette smoking
Change from stratified squamous in gut to glandular epithelium in acid reflux
456
What is aplasia?
Complete failure of tissue or organ to develop
| Organ who's cells wont proliferate
457
What is hypoplasia?
In spectrum with aplasia, it is the incomplete development of an organ or tissue
458
What is involution?
Overlaps with atrophy, it is the normal programmed shrinkage of a tissue eg uterus post birth
459
What is reconstitution?
Replacement of lost body part
460
What is atresia?
Lack of orrifice
461
What is dysplasia?
Abnormal maturation of cells within a tissue, often pre-cancerous
462
What is a neoplasm
Abnormal group of cells that persists after the initial stimulus is removed
463
What is a malignant neoplasm
Abnormal group of cells persisting after initial stimulus removed + invades surrounding tissue with potential to spread
464
What's a tumour?
Clinically detectable lump of swelling
465
What is a neoplasm an example of?
A tumour
466
What is a cancer
Any malignant neoplasm
467
What is a metastasis
A malignant neoplasm that has spread from original site to a non continuos site
468
A pre-neoplasticism alteration in which cells show disordered tissue organisation is what
Dysplasia
469
Why is dysplasia not neoplastic?
The change is reversible
470
Tumours can be dividied into what 2 main categories
Neoplastic and non neoplastic
471
What is important for something to be a benign neoplasm
Confined to original site of origin, doesnt produce metastasis
472
What is important differntiating factor about a malignant neoplastic tumour
It has the potential to metastasise
473
How do benign tumours grow
In a confined local area with pushing outer margins
474
How do malignant tumours grow
Irregular outer margins and may show areas of necrosis and ulceration
475
If something is well differentiated, what does that mean in terms of neoplasm
Closely resembles parent tissue
476
Benign neoplasms have what kind of differentiation
They are well differentiated
477
Malignant neoplasms show what kind of differentiation?
Poorly differentiated
478
What does it mean if a neoplasm is anaplastic
No resemblance to any tissue
479
What features are seen with worsening differentiation in neoplasm?
Increase nuclear size (nuclear to cytoplasm ratio)
Increased nuclear staining (hyperchromasia)
More mitotic figures
Pheomorphism (change in size and shape of cells and nuclei)
480
If a neoplasm is poorly differentiated, what kind of grading is it?
High
481
Mild, moderate and severe dysplasia are measures of what?
Worsening differentiation
482
In mutations you have initiators and promoters. What combination of mutations is needed for neoplasia to develop
Initial mutagenic initiatior followed by promoters of cell proliferation
483
What is progression in relation to neoplasms?
A neoplasm emerging from accumulation of more mutations
484
Are neoplasms monoclonal or polyclonal?
Monoclonal
485
How do we know neoplasms are monoclonal
Studies where lyonisation has occurred (cells that have random allele in cells in mixed tissues)
Neoplastic tissues only express the one isoenzyme
486
In neoplasms, what do the initial genetic alterations affect?
Proto-oncogenes
| Tumour suppressor genes
487
How are proto-oncogenes affected in neoplasia
They become abnormally activated, then known as oncogenes
488
How are tumour suppressor genes altered to favour neoplasm formation
They become inactivated
489
What do benign neoplasms end in?
Oma
490
What do malignant neoplasms end in if they are epithelial
Carcinoma
491
What do malignant neoplasms get called if it is stromal
Sarcoma
492
What is a carcinoma known as if it doesnt invade epithelial basement membrane
In situ
493
If a carcinoma penetrate the basement membrane what is it
Invasive
494
What's leukaemia?
Malignant neoplasms of blood forming cells arising in the bone marrow
495
What are lymphomas
Malignant neoplasms of lymphocytes, mainly affecting lymph nodes
496
What is a myeloma
Malignant neoplasm of plasma cells
497
What do germ cell neoplasms arise from
Pluripotent cells mainly in testis and ovary
498
What's a blastoma?
Neoplasms mainly in children from immature precursor cells
499
What would a benign fat neoplasm get termed
Lipoma
500
What would a benign nerve neoplasm get termed
Neuroma
501
What would a benign cartilage neoplasm get called
Chondroma
502
What would a malignant neoplasm of bone get called
Osteosarcoma
503
What can increase tumour burden
The ability of malignant cells to invade distant sites
504
What is the 3 step process if invasion and metastasis and what do they need to avoid at all points
1. Grow and invade primary
2. Enter a transport system and lodge at secondary
3. Grow and form colonisation
At all points avoiding destruction by immune cells
505
What 3 important alterations do carcinoma cells require to invade into surrounding tissues?
Altered adhesion
Stromal proteolysis
Motility
506
If a carcinoma cell gets the ability to adhere, be motile and have stromal proteolysis what cell phenotype does it more closely resemble. What therefore is this transition called?
Mesenchymal
| Epithelial- mesenchymal transition EMT
507
What cells does a malignant neoplastic cell have to avoid from the immune system?
NKC
| CD8
508
Altered adhesion between malignant cells involves what?
Reduction in E- Catherine expression
509
Altered adhesion between malignant and stromal cells involves what?
Change in integrin expression
510
How does a malignant cell degrade basement membrane and stroma in order to invade a site?
Altered expression of proteases. Notably matrix metalloproteinases MMPs
511
What is a cancer niche?
When malignant cells take advantage of non-neoplastic cells that provide growth factors and proteases.
512
What does altered motility in a malignant cell involve?
Change in the actin skeleton
513
What are the 3 routes that malignant cells can be transported in?
Blood vessels- capillaries and venules
Lymphatic vessels
Fluid in body cavities (pleura, peritoneal, pericardial, brain ventricles)
514
What is transcoelomic spread
Travel via fluid in body cavities of malignant cells
515
What is the greatest barrier to successful formation of metastasis
Failed colinisation
516
What are micrometastases
These are surviving microscopic deposits that fail to grow into mets at distant sites
517
What is tumour dormancy and what can it result in?
It's the apparent disease free person harbouring micro mets
| These are typically causes of relapses years after apparent cure
518
What are the 2 main determinants of where a secondary neoplasm ends up
The regional drainage of the area
| The seed and soil phenomenon
519
In terms of secondary neoplasm. In regional drainage, where would the spread be from lymphatic metastisis?
The the draining lymph node of the site
520
In transcoelemic spread of mets, what is the likely met site?
Adjacent organs
521
In blood borne spread of mets, what is typically the region of the met?
To the next capillary bed
522
What is the seed soil phenomena and what does it help explain
```
The interaction (niche) between certain malignant cells and the environment
Helps explain the seemingly unpredictable nature of blood borne mets?
```
523
What route do carcinomas tend to spread in first?
Lymphatics
524
How do sarcomas tend to spread
In the blood stream
525
Where are common sites of blood borne mets?
Lung
Bone
Liver
Brain
526
What neoplasms frequently spread to bone mets?
Breast, bronchus, kidney, thyroid, prostate
527
What malignant neoplasm is very aggressive and metastisie early?
Small cell bronchial carcinoma
528
What cancer rarely metastisies?
Basal cell carcinoma of skin
529
What is the likelihood of mets based on?
Size of the primary neoplasm
530
How can effects of neoplasms on host be divided?
Direct local effects and indirect systemic effects
531
What are the local effects of primary and secondary neoplasms?4
Direct invasion and destruction of normal tissue
Ulceration at a surface leading to bleeding
Compression of adjacent structures
Blocking of tubes and orifices
532
What are some of the systemic effects of neoplasms
Tumour burden
Secreted factors such as cytokines, both lead to weight loss malaise, thrombosis and immunosupression
Hormone secretion
533
What neoplasms commonly secrete hormones
Neoplasms of endocrine glands
534
What are some of the more miscelannious systemic effects that neoplasms may cause
```
Neuropathies affecting brain and peripheral nerves
Skin problems like pruritis
Abnormal pigmentation
Fever
Finger clubbing
Myositis
```
535
What is exophytic growth?
Tending to grow outward beyond the surface epithelium
536
What is endophytic growth?
Tending to grow inwards towards tissue
537
What is a sarcoma?
Malignant tumour of connective tissue
538
What does anaplastic mean?
Poor cellular differentiation, losing characteristic of mature cells and there orientation with respect to each other and to endothelial cells
539
What is an adenocarcinoma?
Malignant tumour from glandular tissue
540
What is a leiomyoma
Benign smooth muscle tumour
541
What is a leiomyosarcoma?
Smooth muscle connective tissue tumour
542
What is a lymphoma
A group of white blood cell tumours that develops from lymphocytes
543
What are the 2 main categories of lymphoma?
Hodgkin's and non hodgkins
544
What makes it a Hodgkin's lymphoma?
Prescence of reed sternburg cells
545
What does polyploidy mean?
More than 2 paired sets of chromosomes
546
What does sessile mean?
Attached directly via broad base
