PATHOLOGY Flashcards
1
Q
What is acute inflammation?
A
Initial and often transient series of tissue reactions to injury, it’s got a sudden onset, short lived and usually resolves on its own
2
Q
Causes of acute inflammation
A
Microbial infections Hypersensitivity reactions Physical agents Chemicals Tissue necrosis
3
Q
Clinical features of acute inflammation
A
Redness (rubor) Heat (calor) Swelling (tumor) Pain (dolor) Loss of function
4
Q
What makes up the cellular exudate for acute inflammation?
A
Neutrophil polymorphs
Macrophages
Lymphocytes
5
Q
Give an example of acute inflammation
A
Acute appendicitis
6
Q
Give a benefit of inflammation.
A
Inflammation can destroy invading micro-organisms and can prevent the spread of infection.
7
Q
What are the outcomes of acute inflammation?
A
Resolution
Suppuration
Organisation (fibrosis)
Progression to chronic inflammation
8
Q
What are the negatives of acute inflammation?
A
Autoimmunity
When it’s an over-reaction to the stimulus
Fibrosis resulting from chronic inflammation
9
Q
What is chronic inflammation?
A
Subsequent and often prolonged tissue reactions following the initial response, it has a slow onset, long duration and may never resolve
10
Q
Causes of chronic inflammation
A
Primary chronic inflammation
Transplant rejection
Progressing from acute inflammation
Recurrent episodes of acute inflammation
11
Q
Causes of primary chronic inflammation
A
Exogenous materials
Endogenous materials
Resistance of infective agent to phagocytosis and intracellular killing – TB
Autoimmune diseases – rheumatoid arthritis
Primary granulomatous diseases – Crohn’s
12
Q
What is the cellular exudate in chronic inflammation mainly made of?
A
Lymphocytes
Plasma cells
Macrophages
Fibroblasts
13
Q
What is a granuloma?
A
Group of epitheloid histiocytes which can contain lymphocytes and histolytic giant cells
Can cause caseous necrosis
14
Q
Give an example of a granulomatous disease.
A
Tuberculosis
Leprosy
Sarcoidosis
15
Q
How can you treat inflammation?
A
Aspirin, ibuprofen (NSAIDs)
Corticosteroids
16
Q
What is resolution?
A
Initiating factor removed, and tissue is undamaged or able to regenerate
17
Q
What is repair?
A
Initiating factor is still present, and tissue is damaged and unable to regenerate
18
Q
Which organ is a good example for resolution?
A
Liver
19
Q
What affects resolution of the liver?
A
Cirrhosis (ongoing damage resulting in abnormal architecture)
20
Q
Name 5 types of cells capable of regeneration.
A
Hepatocytes Pneumocytes All blood cells Gut epithelium Skin epithelium Osteocytes
21
Q
Name 2 types of cells that are incapable of regeneration.
A
Myocardial cells
Neurones
22
Q
What happens after a skin abrasion?
A
Only top cell layer is removed, leaving the bottom layer/follicles/glands for scab to form and for the epidermis to eventually be regenerated
23
Q
What are the 2 types of skin wound healing?
A
Healing by 1st intention (+ve)
Healing by 2nd intention (-ve)
24
Q
When does 1st intention healing occur?
A
Incision wound
25
How does healing by 1st intention work?
Edge to edge healing (heals w/ reasonable scar)
Fibrinogen exudation
Both ends are sealed together, the slight gap is filled with blood, fibrin etc which holds together a little with stitches
Epidermis regrows, fibroblasts produce collagen
Small scar forms
26
When does 2nd intention healing occur?
When tissue loss has occurred (2 edges can't be brought together nicely)
27
How does 2nd intention healing work?
Infection or haemorrhage prevent healing by first intention
Loss of tissue, granulation tissue forms and organisation occurs (phagocytosis of any debris)
Epithelial regeneration and early fibrous scar
Scar contradiction
28
What is organisation?
Repair of specialised tissue by the formation of a fibrous scar
29
How does organisation occur?
Granulation tissue is formed and dead tissue is removed by phagocytosis
Granulation tissue contracts and accumulated collagen to form a scar
30
What produces collagen?
Fibroblasts
31
Name 3 places where repair occurs and after what
Heart after an MI
Brain after a cerebral infarction
Spinal cord after trauma
32
What is a thrombosis?
Solid mass of blood constituents formed within intact vascular system during life
33
What is Virchow's triad?
Factors that can lead to thrombosis formation:
1. Change in vessel wall
2. Change in blood flow (laminar --> turbulent)
3. Change in constituents of blood
34
What does Virchow's triad do?
Predisposes to thrombosis
35
When does an arterial thrombosis normally occur?
When superimposed on atheroma
36
How does an arterial thrombus occur?
Vessel wall damage
Laminar flow disruption
Collagen exposed
Platelets stick to collagen and aggregate - positive feedback
Rbc’s can get trapped - thrombus formation and fibrin deposition (fibrinogen --> fibrin by platelet factors)
Fibrin mesh holds it all together
Thrombus can then build up and occlude artery
37
What is a vein thombus most commonly due to?
Stasis
38
What are the outcomes of a thrombus?
1. Lysis and resolution
2. Organisation – into a scar
3. Recanalisation – scar and residual thrombus
4. Embolism – breaks off
39
How can you prevent a thrombus?
Exercise
Compression stockings
Aspirin – anti platelet drug, makes endothelial cells less sticky, not a full-blown thrombus occurs
40
What does an occlusion of a coronary artery result in?
Myocardial infarction
41
What does occlusion of a cerebral artery result in?
Cerebral infarction (stroke)
42
What is laminar flow? and why is it important?
Cells travel in the centre of arterial vessels and don't touch arteries - this is important in reducing risk of blood clots
43
What is an Embolus?
Mass of material in the vascular system able to become lodged within vessel and block it
44
What is the most common cause of an embolus?
Piece of thrombus breaking off and getting lodged in a smaller vessel
45
What is the most common occurrence of an embolus?
Pulmonary embolism from deep leg vein thrombosis
46
What is Ischaemia?
Reduction in blood flow
47
What is Infarction?
Death of cells due to reduction in blood supply
48
What is infarction normally caused by?
Thrombosis of an artery
49
Explain a reperfusion injury
Occurs after ischaemia
Blood supply severely limited but cells don’t actually die
Blood flow re-established (reactive hyperaemia - cells overwhelmed with O2)
ROS production that cause damage to tissue and inflammatory response
50
Name organs with 2 blood supplies
Lungs - bronchial arteries and pulmonary arteries
Liver - portal vein and hepatic artery
Some parts of the brain
51
What areas are most susceptible to infarction?
Watershed territories
52
What are the functions of histamine?
```
Vasodilation
Emigration of neutrophils (chemotaxis)
Increase vascular permeability
Pain
Itching
```
53
Role of plasma factors
Complement system
Kinin system
Coagulation cascade (pro-clotting)
Fibrinolytic system (anti-clotting)
54
What is the microscopic appearance of chronic inflammation?
Chronic ulcer
Abscess cavity
Granulatomous inflammation
Fibrosis
55
What is a histiocytic giant cell?
Indeigestible foreign material causes macrophages to fuse together - multinucleate giant cells
Can collect and form granulomas
56
Causes of an embolus
```
Air injected
Thrombus/atheroma
Amniotic fluid
Fat
Tumour
```
57
What happens in a venous system embolism?
Goes to RHS heart
Pulmonary system
Pulmonary embolism
58
What happens in an arterial system embolism?
Goes to LHS heart
Systemic system
Embolism anywhere
59
What is end arterial supply?
Single artery supplies organ - more susceptible to infarction
60
What are watershed territories?
Parts of the brain the have a dual blood supply, but low BP can cause ischaemia
61
What is an atherosclerosis?
Build up of plague in arteries , narrows arteries
62
Where are atherosclerosis' found?
Systemic arterial system - high pressure systems
63
What are the components of an atheroma?
Fibrous cap
Cholesterol and lipid core
Smooth muscle cells surrounded by foam cells
Macrophages
64
Risk factors for atherosclerosis
Smoking - free radicals, nicotine, CO
Hypertension - increased shearing forces
Diabetes - superoxide anions and glycosylation products
Hyperlipidaemia - lipids
Increasing age
Male gender
65
What do the risk factors for atherosclerosis do?
Damage the endothelial cells
66
Explain the pathogenesis of atherosclerosis
1. Endothelial cell damage – see risk factors
2. Repeated endothelial damage -> multiple thrombi -> aggregation -> atheroma formation
3. Vascularised plaque can haemorrhage – propagates atheroma formation
67
What are the complications of atherosclerosis?
Cerebral/myocardial infarct
AAA --> weakens aorta and leads to aortic rupture
Peripheral vascular disease - gangrene
68
How can you treat atheroma?
Aspirin - anti platelet drug
Statins - lower cholesterol
Diet, exercise, control of blood pressure, smoking cessation, weight loss
69
Define apoptosis
Programmed cell death
70
Define necrosis
Traumatic cell death
71
What types of DNA damage cause apoptosis to occur?
Single/double stand break
Base alteration
Cross linking
72
Explain mechanism of apoptosis
1. P53 (gatekeeper of genome) detects DNA damage -> acts as switch for apoptosis
2. Bcl2 and Fas ligand receptor signal for capsases -> apoptosis
3. Membrane bound cell fragments engulfed by macrophages
73
Example of normal apoptosis
Removal of finger webbing during development
74
What can a lack of apoptosis cause?
Cancer - mutation in p53 means cell damage isn't detected
75
In what is excess apoptosis present?
HIV mediated T cell destruction
76
Give examples of necrosis
Myocardial/cerebral infarction
Avascular necrosis of bone - scaphoid or head of femur break
Caseous necrosis - pathological sign of TB
77
Define hypertrophy
Increase in size of a tissue caused by an increase in size of the constituent cells (eg skeletal muscle)
78
Define hyperplasia
Increase in size of a tissue caused by an increase in number of the constituent cells (eg. enlarged prostate)
79
Define atrophy
Decrease in size of tissue caused by a decrease in number of the constituent cells or a decrease in their size (eg. underuse of muscle, Alzheimers)
80
Define metaplasia
Change in differentiation of a cells from one fully differentiated type to a different fully differentiated type (eg. lung cancer - ciliated columnar --> squamous epithelium)
81
Define dysplasia
Imprecise term for the morphological changes seen in cells in the progression to becoming cancer
82
Explain spina bifida
Lack of vertebrae formation - spinal cord is exposed
| Myelomeningocele is the most severe - nerves and meninges bulge out of the back
83
What are other examples of developmental conditions?
Cleft lip/palate - cells fail to migrate and join
| Ventricular septal defect (VSD)
84
Name 3 types of development
Congenital
Inherited
Acquired
85
What is congenital development?
Present at birth - can be inherited or acquired
86
What is inherited development?
Genetic abnormality
87
What is acquired development?
Caused by external/environmental factors
88
Give an example of a chromosomal condition
Down's syndrome - trisomy 21
89
What occurs in Down's syndrome?
Increased beta amyloid production
| Causes early dementia and increase cataract risk
90
Why do growth disorders occur?
Growth hormone deficiency or excess caused by pituitary adenoma
91
Give an example of a growth disorder due to a:
1. Deficiency in GH
2. Excess of GH
1. Dwarfism
| 2. Acromegaly - increased extremity size
92
What is a telomere?
Regions at the end of a chromosome that count the number of cell replication
93
What happens to a telomere as you age?
Telomeres get shorter
94
How can age-related cell damage happen?
Free radical generation and peroxidation of cell membrane
Cross linking of DNA/proteins
Loss of Ca influx control --> mitochondrial damage
accumulation of toxic by-products
95
Explain dermal elastosis
UVB lights causes cross linking of protein (collagen) so damages cells
low elastic properties of skin = wrinkles
96
Explain osteoporosis
Decrease in normal bone matrix caused by lack of oestrogen
| Increase bone resorption and decreased bone formation
97
Why does cataracts occur?
UVB light causes lens protein cross linkage --> crystallin production --> clouding of lens
98
Why does senile dementia occur?
Cortical atrophy
| Plague and neurofibrillary tangle formation
99
What is sarcopenia?
Skeletal muscle atrophy
| Caused by decreased GH, decreased testosterone and increased catabolic cytokines
100
How does deafness occur?
Damage and subsequent loss of cochlear hair cells
101
Does apoptosis or necrosis cause an inflammatory response?
Necrosis
102
Name 5 types of necrosis
```
Caseous necrosis
Coagulative necrosis
Colliquative necrosis
Fibrinoid necrosis
Fat necrosis
```
103
Where is caseous necrosis seen?
It is a pathological sign of tuberculosis
104
What is coagulative necrosis?
Cells become firm and pale
| Seen in most tissues
105
What is colliquative necrosis?
Dead area is liquefied
| Seen in brain
106
What is fibrinoid necrosis a microscopic feature of?
Malignant hypertension - in arterioles
107
What can cause necrosis?
Ischaemia
Metabolic
Trauma
108
What is the hayflick phenomenon?
Number of times a normal human cell population will divide before cell division stops
109
What is a BCC caused by?
UVB light
110
Does a BCC metastasise?
BCC only invade locally
111
How can you treat a BCC
Complete local excision = cure
112
What lymph nodes to carcinomas spread to?
The lymph nodes that drain the site of the carcinoma (e.g. breast cancer --> ancillary lymph nodes)
113
What is leukaemia?
Tumour of WBC, circulates around the body
114
Name 5 cancers that commonly spread to bone
1. Breast
2. Thyroid
3. Kidney
4. Lung
5. Prostate
115
Give symptoms of leukaemia
```
Weight loss
Fever
Frequent infections
Fatigue and loss of appetite
Easy SOB
Night sweats
Easy bleeding and bruising
```
116
How can you confirm a breast cancer diagnosis?
Mammogram or a needle core biopsy
117
Treatment for breast cancer that has NOT spread
Remove tumour --> mastectomy
118
If axillary nodes are affected, how do you know and what treatment should be done?
Confirm by ultrasound and needle core biopsy and then remove any affected axillary nodes
119
What treatment is used if breast cancer has metastasised?
Chemo and radiotherapy
120
What is adjuvant therapy?
Extra treatment given after surgical excision
121
What is the purpose of adjuvant therapy?
Tries to remove micro-metastases that could be present even if tumour is completed excised
122
Give examples of breast cancer adjuvants
Radiotherapy after lumpectomy
| Anti-oestrogen therapy (tamoxifen) - if oestrogen receptor positive
123
Define carcinogenesis
Transformation of normal cells to neoplastic cells through permanent genetic changes
124
Features of carcinogenesis
Applies to malignant neoplasms
| Multistep process
125
What does oncogenesis refer to?
Benign and malignant tumours
126
Define carcinogen
Mutagenic (act on DNA) agents that cause (or are suspected to cause) tumours
127
What is the difference between carcinogenic and oncogenic?
```
Carcinogenic = cancer causing
Oncogenic = tumour causing
```
128
Name the carcinogen classes
Chemical
Radiation
Biological organisms
Miscellaneous
129
Give examples of chemical carcinogens
Polycyclic aromatic hydrocarbons (smoking, mineral oils) --> lung and skin cancer
130
Give examples of radiation carcinogens
UVA and B --> BCC, melanoma
Ionising radiation --> skin (radiographers – thorium), lung (uranium miners), thyroid cancer (Ukrainian children - Chernobyl nuclear explosion)
131
Give an example of a hormone carcinogen
Increased oestrogen --> mammary and endometrial cancer
132
Give an example of a mycotoxin carcinogen
Mycotoxin (Aflatoxin B1) --> hepatocellular cancer
133
Give an example of a parasite carcinogen
Parasites --> cholangiocarcinoma and bladder cancer
134
Give an example of a viral carcinogen
HPV --> cervical cancer
135
Give an example of a misscellaneous carcinogen
Asbestos --> lung cancer, asbestosis (unknown mechanism of action)
136
Name host factors for carcinogenesis
Race
Constitutional
Premalignant conditions
Transplacental exposure
137
Define tumour
Any abnormal swelling
| Neoplasm, inflammation, hypertrophy and hyperplasia
138
Define Neoplasm
A lesion resulting from the NEW AUTONOMOUS ABNORMAL growth of cells that PERSISTS after removal of initiating stimulus
139
What is the structure of a neoplasm?
Neoplastic cells
| Stroma - connettive tissue framework
140
What does the stroma provide of the neoplasm?
Mechanical support
Nutrition
Intracellular signalling
Contains blood vessels which perfuse the tumour
141
A tumour <2mm is known as a ...?
Avascular nodule
142
How big is a vascularised nodule?
>2mm
143
What happens when there is increased growth in tumour angiogenesis?
Increased growth = central necrosis
144
How can neoplasms be classified?
```
Behavioural = being, malignant
Histogenetic = cell of origin
```
145
Features of benign neoplasms
Localised and on-invasive
Slow growth rate - out and up
Close resemblance to normal tissue
146
Problems with benign neoplasms
```
Pressure on adjacent structures
Flow obstruction
Hormone production
Transformation to a malignant neoplasm
Anxiety
```
147
Features of malignant neoplasms
Invasive and metastases
Rapid growth rate - down and in
Poorly defined and irregular borders
148
Problems with malignant neoplasms
```
Tissue destruction
Paraneoplastic effects (symptoms not just due to cancer at the site) - weight loss
Metastasise
Pressure on adjacent structures
Flow obstruction
Hormone production
Anxiety and pain
```
149
What is the suffix for neoplasms?
-oma
150
What neoplasms do epithelial cells form?
Carcinomas
151
What neoplasms do connective tissues form?
Sarcomas
152
What neoplasms do lymphoid/haemopoietic organs form?
Lymphomas or leukaemia
153
What is a papilloma?
A benign non glandular epithelial neoplasm
154
What is an adenoma?
A benign glandular epithelial neoplasm
155
What is a carcinoma?
A malignant non glandular epithelial neoplasm
156
What is a adenocarcinoma?
A malignant glandular epithelial neoplasm
157
Name some benign connective tissue neoplasms
```
Lipoma = adipocytes
Chondroma = cartilage
Osteoma = bone
Angioma = vascular
Rhabdomyoma = striated muscle
Leiomyoma = smooth muscle
Neuroma = nerves
```
158
What is the suffix for malignant connective tissue neoplasms?
-sarcoma
159
Name some malignant connective tissue neoplasms
```
Liposarcoma = adipose tissue
Chondrosarcoma = cartilage
Osteosarcoma = bone
Angiosarcoma = vascular
Rhabdomyosarcoma = striated muscle
Leiomyosarcoma = smooth muscle
```
160
What is graded malignancy?
Carcinomas and sarcomas are further classified according to degree of differentiation (how much it resembles normal tissue)
161
What are the types of grade of malignancy?
Low grade – looks like parent tissue (well differentiated)
High grade – doesn’t look like parent tissue (poorly differentiated)
Anaplastic – unknown origin cell type
162
Name some exceptions to -oma rule
Granuloma
Melanoma - malignant
Lymphoma - malignant
Treatoma
163
What is a carcinoma in situ?
Carcinoma fills cavity but has not invaded any other tissue
164
What are the 8 stages of metastasis?
1. Detachment
2. Invasion
3. Intravasation
4. Evasion
5. Adherence
6. Extravasation
7. Growth
8. Angiogenesis
165
Explain invasion
Some cells go through the basement membrane into the extracellular matrix using enzymes (proteases, collagenase, cathepsin D, urokinase-like plasminogen activator)
166
What is intravasation?
Tumour cells move from ECM to blood/lymph vessels
167
What is evasion?
Aggregate with platelets, shed surface antigens and stick to other tumour cells
168
Explain adherence
Adherence of ells to endothelium at a remote location
169
Explain extravasation
Tumour cells move from vessels to new tissue area
170
What is angiogenesis?
Formation of blood vessels
171
Name 3 routes of metastasis
Haematogenous - by blood stream
Lymphatic
Transoelomic - in pleural, pericardial and peritoneal cavities
172
What tumours commonly metastasise to the lungs?
Most carcinomas and sarcomas (venous --> pulmonary system)
173
What tumours commonly metastasise to the liver?
Colon, stomach, pancreas, intestine (portal system)
174
What tumour never metastasises?
Basal cell carcinoma
175
What term describes a cancer that has not invaded through the basement membrane?
Carcinoma in situ
176
Give 2 promoters of tumour angiogenesis
1. Vascular endothelial growth factors
| 2. Fibroblast growth factors
177
Give 3 inhibitors of tumour angiogenesis
1. Angiostatin
2. Endostatin
3. Vasculostatin
178
Define exudate
A protein rich fluid that leaks out of vessel walls due to increased vascular permeability
179
Give 3 endogenous chemical mediators of acute inflammation
1. Bradykinin
2. Histamine
3. Nitric Oxide
180
The activity of what enzyme in the blood can act as a marker for granulomatous disease?
Angiotensin converting enzyme
181
Define abscess
Acute inflammation with a fibrotic wall
182
what are the steps of acute inflammation?
- Initial reaction of tissue to injury
- Vascular component: dilation of vessels
- Exudative component: vascular leakage of protein-rich fluid
183
what is a rhabdomyoma?
Benign striated muscle neoplasm.
184
what is a sarcoma?
Malignant connective tissue neoplasm.
185
what is a leiomyoma?
A benign smooth muscle neoplasm.
186
what is a neuroma?
A benign neoplasm of nerves.
187
what is a chondrosarcoma?
A malignant neoplasm of cartilage.
188
what is a liposarcoma?
A malignant neoplasm of adipose tissue.
189
what is a melanoma?
A malignant neoplasm of melanocytes.
190
what is a lymphoma?
A malignant neoplasm of lymphoid cells.
191
what is a mesothelioma?
A malignant neoplasm of mesothelial cells.
192
what is the role of p53 protein?
p53 protein looks for DNA damage, if damage is present p53 switches on apoptosis.
193
What protein can switch on apoptosis if DNA damage is present?
p53 protein
194
Activation of which family of protease enzymes can turn on apoptosis?
Caspases.
195
Activation of what receptor can activate caspase and therefore apoptosis?
FAS receptor.
196
What is required for a tumour to enter the blood stream (intravasation)?
1. Collagenases.
| 2. Cell motility.
197
What is required for a tumour to exit the blood stream (extravasation)?
1. Adhesion receptors.
2. Collagenases.
3. Cell motility.
198
What causes the pain associated with acute inflammation?
1. Stretching and distortion of tissues due to oedema and pus under high pressure in an abscess cavity.
2. Chemical mediators e.g. bradykinin and prostaglandins, are also known to induce pain.
199
Describe the process of neutrophil polymorph migration into tissues as seen in acute inflammation.
1. Margination of neutrophils.
2. Pavementing of neutrophils.
3. Neutrophils pass between endothelial cells.
4. Neutrophils pass through basal lamina and migrate into adventitia.
200
Chemical carcinogens: what types of cancer do polycyclic aromatic hydrocarbons cause?
Lung cancer and skin cancer.
201
Chemical carcinogens: what can expose people to polycyclic aromatic hydrocarbons?
Smoking cigarettes and mineral oils.
202
Chemical carcinogens: what types of cancer do aromatic amines cause?
Bladder cancer.
203
Chemical carcinogens: what types of people are more susceptible to bladder cancer caused by aromatic amine exposure?
People who work in the rubber/dye industry.
204
Chemical carcinogens: what type of cancer do nitrosamines cause?
Gut cancer.
205
Chemical carcinogens: what type of cancer do alkylating agents cause?
Leukaemia; the risk is small in humans.
206
Why can cigarette smoking lead to atherosclerosis?
Cigarette smoking releases free radicals, nicotine and CO into the body. These all damage endothelial cells.
