Pathology Flashcards
1
Q
Describe the process of fibrosis
A
dead tissue and exudate are removed by macrophages
defect is filled by specialised vascular connective tissue (granulation tissue)
granulation tissue produces collagen
2
Q
Describe the steps of acute inflammation
A
Initial reaction of tissue to injury -> vascular component = dilation of vessels -> exudative component = vascular leakage of protein rich fluid
3
Q
Give 4 examples of granulomatous disease
A
TB
Leprosy
Crohn’s
sarcoidosis
4
Q
Give 4 examples of primary chronic inflammation
A
glandular fever
IBD
sarcoidosis
RA
5
Q
Give 5 causes of acute inflammation
A
microbial infections hypersensitivity rxns physical agents chemicals bacterial toxins
6
Q
How does a scar form?
A
granulation tissue contracts and gradually accumulates collagen
this then undergoes remodelling
7
Q
What are the essential macroscopic appearances of acute inflammation?
A
erythema heat swelling pain loss of function
8
Q
What are the outcomes of acute inflammation?
A
1 resolution 2 suppuration (abscess) 3 organisation (fibrosis) 4 progression (to chronic inflammation) 5 tissue necrosis
9
Q
What are the systemic effects of inflammation?
A
1 pyrexia 2 constitutional symptoms 3 weight loss 4 reactive hyperplasia of RES 5 AMYLOIDOSIS
10
Q
What cells are predominant in chronic inflammation?
A
lymphocytes, plasma cells, macrophages
11
Q
What cellular component is essential for a histological diagnosis of acute inflammation?
A
the accumulation of neutrophil polymorphs in the extra cellular space
12
Q
What is a granuloma?
A
An aggregate of epithelioid histiocytes (may also contain lymphocytes)
13
Q
What is acute inflammation?
A
the initial and often transient series of tissue reaction to injury. May last few hours to days
14
Q
What is chronic inflammation?
A
The subsequent and often prolonged tissue reaction to injury following the initial response
15
Q
What is granulation tissue?
A
combination of capillary loops and myofibroblasts appearing during repair of specialised/complex tissue
16
Q
What is inflammation?
A
The local physiological response to injury
17
Q
What is the main role of T lymphocytes?
A
On contact with antigen -> produce a range of cytokines which recruit and activate other cell types
18
Q
What is the role of histamine in acute inflammation?
A
chemical mediator ->causes vasodilation and immediate increased vascular permeability
19
Q
What is the role of tissue macrophages in acute inflammation?
A
secrete cytokines (TNF-alpha, IL 1) after histamine and thrombin have acted on endothelial cells
clear away tissue debris and damaged cells
20
Q
What would the presence of granulomas and eosinophils indicate?
A
parasitic infection e.g. worms
21
Q
When does ‘organisation’ happen as a result of acute inflammation?
A
when there is substantial damage to connective tissue/ tissue lacks ability to regenerate specialised cells (FIBROSIS)
22
Q
Where is histamine found?
A
stored in preformed granules in mast cells/basophils/eosinophils/leukocytes/platelets
23
Q
Which chemicals are released early in the response to acute inflammation and what is their function?
A
histmaine and thrombin - neutrophil adhesion to endothelial surface
24
Q
What is a thrombosis?
A
The solidification of blood contents that forms within the vascular system during life
25
What are the three factors that can lead to Thrombosis?
Virchow's triad
- Change in vessel wall
- change in blood flow
- change in blood constituents
26
What are the 4 potential outcomes of having a thrombus?
1 resolution
2 organisation (into scar tissue and consequent lumen narrowing)
3 re-canalisation
4 embolism
27
Define atherosclerosis.
A hardened plaque in the intima of an artery. It is an inflammatory process.
28
What conditions can an atherosclerotic plaque cause?
1. Heart attack.
2. Stroke.
3. Gangrene.
29
What are the constituents of an atheromatous plaque?
1. Lipid core.
2. Necrotic debris.
3. Connective tissue.
4. Fibrous cap.
5. Lymphocytes.
30
Give 5 risk factors for atherosclerosis.
1. Family history.
2. Increasing age.
3. Smoking.
4. High levels of LDL's.
5. Obesity.
6. Diabetes.
7. Hypertension.
31
In which arteries would you be most likely to find atheromatous plaques?
In the peripheral and coronary arteries.
32
Which histological layer of the artery may be thinned by an atheromatous plaque?
The media.
33
What is the precursor for atherosclerosis.
Fatty streaks
34
Describe in 5 steps the progression of atherosclerosis.
1. Fatty streaks.
2. Intermediate lesions.
3. Fibrous plaque.
4. Plaque rupture.
5. Plaque erosion.
35
Progression of atherosclerosis: what are the constituents of fatty streaks?
Foam cells and T-lymphocytes. Fatty streaks can develop in anyone from about 10 years old.
36
Progression of atherosclerosis: what are constituents of intermediate lesions?
- Foam cells.
- Smooth muscle cells.
- T lymphocytes.
- Platelet adhesion.
- Extracellular lipid pools.
37
Progression of atherosclerosis: what are the constituents of fibrous plaques?
- Fibrous cap overlies lipid core and necrotic debris.
- Smooth muscle cells.
- Macrophages.
- Foam cells.
- T lymphocytes.
Fibrous plaques can impede blood flow and are prone to rupture.
38
Progression of atherosclerosis: why might plaque rupture occur?
Fibrous plaques are constantly growing and receding. The fibrous cap has to be resorbed and redeposited in order to be maintained. If balance shifted in favour of inflammatory conditions, the cap becomes weak and the plaque ruptures. Thrombus formation and vessel occlusion.
39
What is the treatment for atherosclerosis?
Percutaneous coronary intervention (PCI).
40
What is the major limitation of PCI?
Restenosis
41
How can restenosis be avoided following PCI?
Drug eluting stents: anti-proliferative and drugs that inhibit healing.
42
What is the key principle behind the pathogenesis of atherosclerosis?
It is an inflammatory process!
43
Define atherogenesis.
The development of an atherosclerotic plaque.
44
Give a benefit of inflammation.
Inflammation can destroy invading micro-organisms and can prevent the spread of infection.
45
Give a disadvantage of inflammation.
Inflammation can produce disease and can lead to distorted tissues with permanently altered function.
46
Define exudate.
A protein rich fluid that leaks out of vessel walls due to increased vascular permeability.
47
What does viral infection result in?
Cell death due to intracellular multiplication.
48
What does bacterial infection result in?
The release of exotoxins (involved in the initiation of inflammation) or endotoxins.
49
Give 3 endogenous chemical mediators of acute inflammation.
1. Bradykinin.
2. Histamine.
3. Nitric Oxide.
50
What cell can form when several macrophages try to ingest the same particle?
Multinucleate giant cell.
51
Give 4 causes of chronic inflammation.
1. Primary chronic inflammation.
2. Transplant rejection.
3. Recurrent acute inflammation.
4. Progression from acute inflammation.
52
What are some macroscopic features of chronic inflammation?
1. Chronic ulcer.
2. Chronic abscess cavity.
3. Granulomatous inflammation.
4. Fibrosis.
53
The activity of what enzyme in the blood can act as a marker for granulomatous disease?
Angiotensin converting enzyme.
54
What is the difference between resolution and repair?
Resolution is when the initiating factor is removed and the tissue is able to regenerate. In repair, the initiating factor is still present and the tissue is unable to regenerate.
55
Name 5 types of cells capable of regeneration.
1. Hepatocytes.
2. Osteocytes.
3. Pneumocytes.
4. Blood cells.
5. Gut and skin epithelial cells.
56
Name 2 types of cells that are incapable of regeneration.
1. Myocardial cells.
| 2. Neuronal cells.
57
Define abscess.
Acute inflammation with a fibrotic wall.
58
Give 2 reasons why thrombosis formation is uncommon.
1. Laminar flow.
| 2. Non sticky endothelial cells.
59
Define embolus.
A mass of material (often a thrombus) in the vascular system that is able to become lodged in a vessel and block it.
60
Define ischaemia.
Decreased blood flow
61
Define infarction
Decreased blood flow with consequent cell death
62
Why are tissues with an end arterial supply more susceptible to infarction?
They only have a single arterial supply and so if this vessel is interrupted infarction is likely.
63
Give 3 examples of organs with a dual arterial supply.
1. Lungs (bronchial arteries and pulmonary veins).
2. Liver (hepatic arteries and portal veins).
3. Some areas of the brain around the circle of willis.
64
Define atherosclerosis.
Inflammatory process characterised by hardened plaques in the intima of a vessel wall.
65
Is atherosclerosis more common in the systemic or pulmonary circulation?
It is more common in the systemic circulation because this is a higher pressure system.
66
What are the 3 main constituents of an atheromatous plaque?
1. Lipids.
2. Fibrous tissue.
3. Lymphocytes.
67
Define aneurysm
A localised permanent dilation of part of the vascular tree
68
What is apoptosis?
Programmed cell death of a single cell without the release of products harmful to surrounding cells
69
What is the role of p53 protein?
p53 protein looks for DNA damage, if damage is present p53 switches on apoptosis.
70
What protein can switch on apoptosis if DNA damage is present?
p53 protein
71
Give an example of a disease where there is a lack of apoptosis.
Cancer; mutations in p53 mean cell damage isn't detected.
72
Give an example of a disease where there is too much apoptosis.
HIV
73
Define necrosis.
Traumatic cell death which induces inflammation and repair
74
Give 3 examples of events that can lead to necrosis.
1. Frost bite.
2. Avascular necrosis.
3. Infarction.
75
Give 3 differences between apoptosis and necrosis.
1. Apoptosis is programmed cell death whereas necrosis is unprogrammed.
2. Apoptosis tends to effect only a single cell whereas necrosis effects a large number of cells.
3. Apoptosis is often in response to DNA damage. Necrosis is triggered by an adverse event e.g. frost bite.
76
Define hypertrophy.
Increase in the size of a tissue due to an increase in the size of constituent cells.
77
Define hyperplasia.
Increase in the size of a tissue due to an increase in the number of constituent cells.
78
Define atrophy.
Decrease in the size of a tissue due to a decrease in the size of the constituent cells OR due to a decrease in the number of constituent cells.
79
Define metaplasia.
A change in the differentiation of a cell from one fully differentiated cell type to another fully differentiated cell type.
80
Give an example of a disease that demonstrates metaplasia.
Barrett's oesophagus - the cells at the lower end of the oesophagus change from stratified squamous cells to columnar.
81
Define dysplasia.
Morphological changes seen in cells in the progression to becoming cancer. The cells become more 'jumbled up'.
82
Give an example of:
a) a dividing tissue.
b) a non dividing tissue.
a) Gut or skin tissue can divide.
| b) Brain tissue is non dividing.
83
Give an example of hypertrophy
Muscular hypertrophy of the left ventricle of the heart (as a response to sustained outflow
resistance)
84
Give an example of hyperplasia
Hyperplasia of prostate smooth muscle either benign or cancerous
85
Give an example of atrophy
Loss of innervation of muscle causes muscle atrophy
86
What happens to a cell when the telomere gets too short?
It can no longer divide.
87
Define carcinoma.
MALIGNANT EPITHELIAL NEOPLASM
88
Give an example of 5 carcinoma's that can spread to bone.
1. Breast.
2. Kidney.
3. Lung.
4. Prostate.
5. Thyroid.
89
Why is adjuvant therapy often used in the treatment of carcinomas?
Micrometastes are possible even if a tumour is excised and so adjuvant therapy is given to suppress secondary tumour formation.
90
What is required for a tumour to invade through a basement membrane?
1. Proteases.
| 2. Cell motility.
91
What is required for a tumour to enter the blood stream (intravasation)?
1. Collagenases.
| 2. Cell motility.
92
What is required for a tumour to exit the blood stream (extravasation)?
1. Adhesion receptors.
2. Collagenases.
3. Cell motility.
93
Give 4 characteristics of neoplastic cells
- Derive from nucleated cells
- Usually monoclonal
- Growth pattern is related to the parent cell
- They continue to synthesise or secrete cell products such as collagen, mucin or keratin; these often accumulate within the tumour
94
How are tumours classified?
Behaviourally or Histiogentically
95
Give 2 promoters of tumour angiogenesis.
1. Vascular endothelial growth factors.
| 2. Fibroblast growth factors.
96
What 3 mechanisms do tumour cells use to evade host immune defence in the blood?
1. Platelet aggregation.
2. Adhesion to other tumour cells.
3. They shed surface antigens so as to 'distract' lymphocytes.
97
Give an example of a malignant tumour that often spreads to the lung.
Sarcoma (via venae cavae -> heart -> pulmonary arteries).
98
What is the role of the lymphatic system in acute inflammation?
Lymphatic channels dilate and drain away oedematous fluid therefore reducing swelling. Antigens are also carried to lymph nodes for recognition by lymphocytes.
99
What is the major role of neutrophil polymorphs in acute inflammation?
Phagocytosis!
100
Define carcinogenesis.
A multistep process in which normal cells become neoplastic cells due to mutations.
101
What percentage of cancer risk is due to environmental factors?
85% environmental, 15% genetic.
102
Define neoplasm.
An autonomous, abnormal, persistent new growth.
103
What is a neoplasm composed of?
1. Neoplastic cells.
| 2. Stroma.
104
Describe the stroma of a neoplasm.
Connective tissue composed of fibroblasts and collagen; it is very dense. There is a lot of mechanical support and blood vessels provide nutrition for the neoplastic cells.
105
What is essential for neoplasm growth?
Angiogenesis.
106
What is the behavioural classification of neoplasms?
Neoplasms can be classified as benign, malignant or borderline. Borderline tumours (e.g. some ovarian lesions) defy precise classification.
107
What is the histogenetic classification of neoplasms?
Histopathological tests specify tumour type by determining the cell of origin of a tumour. If the origin is unknown the tumour is said to be anaplastic.
108
What are the 7 main features of benign neoplasms.
1. Localised.
2. Non-invasive.
3. Slow growth, low mitotic activity.
4. Close resemblance to normal tissue.
5. Normal nuclei.
6. Necrosis and ulceration are rare due to slow growth.
7. Exophytic growth.
109
What are the consequences of benign neoplasms?
1. Pressure on adjacent structures.
2. Obstruction to flow.
3. Transformation into malignant neoplasms.
4. Anxiety.
110
What are the 7 main features of malignant neoplasms.
1. INVASIVE!
2. Metastases.
3. Rapid growth, high mitotic activity.
4. Resemblance to normal tissue.
5. Poorly defined border due to invasive nature.
6. Necrosis and ulceration are common.
7. Endophytic growth.
111
What are the consequences of malignant neoplasms?
- Destroy surrounding tissue
- Blood loss due to ulceration
- Pain
- Anxiety.
112
Define sarcoma.
Malignant connective tissue neoplasm.
113
What is an adenoma?
Benign tumour of glandular epithelium.
114
What is a papilloma?
A non-glandular benign tumour.
115
Carcinomas and sarcomas are further classified according to the degree of differentiation. Is a carcinoma/sarcoma with a close resemblance to normal tissue classified as well differentiated or poorly differentiated?
A carcinoma/sarcoma with a close resemblance to normal tissue is classified as well differentiated. These types of neoplasms are low grade and have a better prognosis.
116
Define adenocarcinoma.
A malignant neoplasm of glandular epithelium.
117
Describe adaptive immunity
Immune response specific to antigen, therefore is quicker.
Requires the use of lymphocytes
118
Describe innate immunity
Non-specific immune response
instinctive
present from birth
first line of defence.
It is focused around physical and chemical barriers and phagocytosis. No lymphocyte involvement.
119
Give examples of physical and chemical barriers used in innate immunity?
Skin, mucociliary escalator, gastric acid, hairs, lysozymes etc.
120
Describe the first immune response to initial exposure.
1. Innate immune response.
2. IgM predominates.
3. Low affinity.
121
Define allergy. Give example
An abnormal response to harmless foreign material. e.g. allergic rhinitis (hay fever)
122
Define hypersensitivity. Give example
Undesirable reaction produced by normal immune system. e.g. anaphylaxis
123
Define immunodeficiency. Give example
Ability of immune system to fight infectious disease/cancer is compromised.
(AIDS - acquired immunodeficiency disorder)
124
Describe the second immune response following exposure to a pathogen encountered before.
1. Rapid and larger than the first.
2. High affinity IgG.
3. Adaptive immunity, T cell help.
125
Give examples of 3 polymorphonuclear leukocytes.
1. Neutrophils.
2. Basophils.
3. Eosinophils.
126
Give examples of 3 mononuclear leukocytes.
1. Monocytes.
2. B lymphocytes.
3. T lymphocytes.
127
How do T cells recognise antigens?
For T cells to recognise antigens they must be displayed by an antigen presenting cell and bound to MHC1/2. T cells can't recognise soluble antigens.
128
What is the function of T helper (CD4+) cell?
Release cytokines
| Produces antibodies against pathogens
129
What is the function of cytotoxic (CD8+) cell?
It can kill cells directly by binding to antigens; they induce apoptosis.
130
Which cells express MHC2?
Antigen presenting cells ONLY e.g. macrophages, B cells, dendritic cells. (presented to CD4+ cells)
131
What type of T cell binds to MCH1?
CD8+
132
What do B cells differentiate into?
Plasma cells. The plasma cells then produce antibodies.
133
Describe the process of a T helper cell binding to a B cell.
A B-cell antibody binds an antigen -> phagocytosis -> epitope is displayed on the surface of the B-cell bound to an MHC2 -> TH2 binds to B-cells -> cytokine secretion induces B-cell clonal expansion -> differentiation into plasma cells and memory B cells.
134
Give 3 functions of antibodies.
1. Neutralise toxins.
2. Opsonisation.
3. Activate classical complement system.
135
Name 4 types of cytokines.
1. Interferons.
2. Interleukins.
3. Colony stimulating factors.
4. Tumour necrosis factors.
136
What is the function of interferons?
Interferons produce antiviral proteins.
137
What is the function of interleukins?
Interleukins cause cell division and differentiation.
138
What is the function of colony stimulating factor (CSF)?
CSF causes division and differentiation of bone marrow stem cells.
139
What is the function of tumour necrosis factor (TNF)?
TNF mediates inflammation and cytotoxic reactions.
140
What is the function of chemokines?
Chemokines attract leukocytes to sites of infection.
141
Give examples of secondary lymphoid tissue.
The spleen, lymph nodes, mucosa associated lymphoid tissue - MALT.
142
Give 3 examples of O2 dependent mechanisms of killing.
1. Killing using reactive oxygen intermediates.
2. Superoxides can be converted to H2O2 and then to hydroxyl free radicals.
3. NO leads to vasodilation and increased extravasation and so more neutrophils etc are in the tissues to destroy pathogens.
143
What kind of immunity are PRR's and PAMP's associated with?
Innate immunity.
144
What happens when a PAMP binds to a PRR?
The innate immune response and inflammatory response is triggered.
145
What are the 7 hallmarks for cancer?
1. Evade apoptosis.
2. Ignore anti-proliferative signals.
3. Growth and self sufficiency.
4. Limitless replication potential.
5. Sustained angiogenesis.
6. Invade surrounding tissues.
7. Escape immuno-surveillance.
146
Give 3 advantages of transplantation.
1. Improved quality of life.
2. Improves survival rates.
3. Cost effective.
147
What are the 5 features of an ideal vaccine?
1. Safe.
2. Induces a suitable immune response.
3. Shouldn't require repeated boosters.
4. Generates immunological memory.
5. Stable and easy to transport.
148
What are the different types of autopsy?
Hospital (10%)
| Medico-legal: coronial/forensic(90%)
149
What is the role of the coronial autopsy?
```
To answer
• Who was the deceased?
• When did they die?
• Where did they die?
• How did their death come about?
```
150
Why are deaths referred to the coroner?
- presumed natural (not seen Dr for 2 weeks prior, not previously unwell)
- presumed iatrogenic ( peri/postoperative deaths etc)
- presumed unnatural ( suicide, accident, neglect)
151
Who refers deaths to the coroner?
- Drs
- police
- registrar of Births, Deaths, Marriages
- relatives
152
Who carries out autopsies?
- histopathologist
| - forensic pathologist (homocide, 3rd party involvement, neglect etc)
153
What is atopy?
The tendency to develop allergies.
154
Which immunoglobulin is most commonly involved in allergic responses?
IgE
155
Which cells are most commonly involved in allergic responses?
Mast cells! Also eosinophils and basophils.
156
What happens to IgE receptors when a 'threat' is identified?
The receptors cross-link.
157
Which cells express high affinity IgE receptors?
Mast cells, basophils and eosinophils.
158
What are the steps in an allergic response?
Allergen/threat is identified -> high affinity IgE receptors cross link -> IgE binds -> Mast cells are activated -> granules released -> histamine and cytokines. Cytokines induce a TH2 response.
159
What is the main IgE receptor cell?
MAST CELLS!
160
Which compound causes blood vessel dilation and vascular leakage in an allergic response?
Histamine.
161
What is the role of cytokine release in an allergic response?
They induce a TH2 response.
162
Which cells and which immunoglobulin is commonly involved in anaphylaxis?
- Mast cells and basophils.
| - IgE.
163
Give examples of anaphylactic systemic effects.
- CV: vasodilation, lowered BP.
- Resp: bronchial SM contraction, mucus.
- Skin: rash, swelling.
- GI: pain, vomiting.
164
Give 5 possible treatments for allergy and hypersensitivity.
1. Avoid allergens.
2. Desensitisation (immunotherapy, some risks).
3. Prevent IgE production (interfere with TH2 pathway).
4. Prevent mast cell activation.
5. Inhibit mast cell products (e.g. histamine receptor antagonists).
165
What is anaphylaxis?
an acute allergic reaction to an antigen to which the body has become hypersensitive
166
Describe type 1 hypersensitivity.
IgE mediated hypersensitivity. Acute anaphylaxis. IgE becomes attached to mast cells, IgE cross linking leads to mast cell degranulation -> histamine.
167
Describe type 2 hypersensitivity.
IgG mediated cytotoxicity.
168
Describe type 3 hypersensitivity.
Immune complex deposition; immune complexes have not been adequately cleared by innate immune cells, giving rise to an inflammatory response.
169
Describe type 4 hypersensitivity.
T cell mediated.
170
Give 6 features of anaphylaxis.
1. Rapid onset.
2. Blotchy rash.
3. Swelling of face and lips.
4. Wheeze.
5. Hypotension.
6. Cardiac arrest if severe.
171
What can cause a type 1 hypersensitivity reaction?
Pollen, cat hairs, peanuts etc. (allergies).
172
What can cause a type 2 hypersensitivity reaction?
Transplant rejection.
173
What can cause a type 3 hypersensitivity reaction?
Fungal
174
What can cause a type 4 hypersensitivity reaction?
TB
175
What is the treatment for anaphylaxis?
1. Commence basic life support (ABC).
2. Stop infusion of drug.
3. Give adrenaline and anti-histamines.
176
Give 4 risk factors for hypersensitivity.
1. Protein based macromolecules.
2. Female > male.
3. Immunosuppression.
4. Genetic factors.
