Introductory Clinical Sciences Flashcards
(620 cards)
1
Q
Define inflammation.
A
A local physiological response to tissue injury.
2
Q
Give a benefit of inflammation.
A
Inflammation can destroy invading micro-organisms and can prevent the spread of infection.
3
Q
Give a disadvantage of inflammation.
A
Inflammation can produce disease and can lead to distorted tissues with permanently altered function.
4
Q
Define exudate.
A
A protein rich fluid that leaks out of vessel walls due to increased vascular permeability.
5
Q
What are the 4 outcomes of inflammation?
A
- Resolution.
- Suppuration.
- Organisation (scar tissue formation).
- Progression onto chronic inflammation.
6
Q
Give 6 causes of acute inflammation.
A
- Microbial infections (bacteria and viruses).
- Chemicals (corrosives, acids/alkalis).
- Physical agents (trauma, burns, frost bite).
- Hypersensitivity reactions (TB).
- Bacterial toxins.
- Tissue necrosis.
7
Q
What does viral infection result in?
A
Cell death due to intracellular multiplication.
8
Q
What does bacterial infection result in?
A
The release of exotoxins (involved in the initiation of inflammation) or endotoxins.
9
Q
Give 5 cardinal signs of Acute inflammation.
A
- Redness (rubor).
- Swelling (tumor).
- Pain (dolor).
- Heat (calor).
- Loss of function.
10
Q
How can acute inflammation be diagnosed histologically?
A
By looking for the presence of neutrophil polymorphs.
11
Q
Give 3 endogenous chemical mediators of acute inflammation.
A
- Bradykinin.
- Histamine.
- Nitric Oxide.
12
Q
What are 4 systemic effects of acute inflammation?
A
- Fever.
- Feeling unwell.
- Weight loss.
- Reactive hyperplasia of the reticuloendothelial system.
13
Q
What cells are involved in chronic inflammation?
A
Macrophages and plasma cells (B and T lymphocytes).
14
Q
What cell can form when several macrophages try to ingest the same particle?
A
Multinucleate giant cell.
15
Q
Give 4 causes of chronic inflammation.
A
- Primary chronic inflammation.
- Transplant rejection.
- Recurrent acute inflammation.
- Progression from acute inflammation.
16
Q
Give examples of primary chronic inflammation.
A
- Infective substances having resistance to phagocytosis e.g. TB, leprosy.
- Endogenous materials e.g. uric acid crystals.
- Exogenous materials e.g. asbestos.
- Autoimmune diseases e.g. chronic gastritis, rheumatoid arthritis etc.
- Other chronic inflammatory diseases e.g. chronic inflammatory bowel disease.
17
Q
In which type of inflammation would you see neutrophil polymorphs?
A
Acute inflammation.
18
Q
What are some macroscopic features of chronic inflammation?
A
- Chronic ulcer.
- Chronic abscess cavity.
- Granulomatous inflammation.
- Fibrosis.
19
Q
What is granulation tissue?
A
Granulation tissue is composed of small blood vessels in a connective tissue matrix with myofibroblasts. It is important in healing and repair.
20
Q
Define granuloma.
A
An aggregate of epithelioid histocytes.
21
Q
Give an example of a granulomatous disease.
A
TB, leprosy, Crohn’s disease and sarcoidosis.
22
Q
The activity of what enzyme in the blood can act as a marker for granulomatous disease?
A
Angiotensin converting enzyme.
23
Q
What kind of disease is TB?
A
A granulomatous disease.
24
Q
What is the difference between resolution and repair?
A
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.
25
Name 5 types of cells capable of regeneration.
1. Hepatocytes.
2. Osteocytes.
3. Pneumocytes.
4. Blood cells.
5. Gut and skin epithelial cells.
26
Name 2 types of cells that are incapable of regeneration.
1. Myocardial cells.
| 2. Neuronal cells.
27
Define abscess.
Acute inflammation with a fibrotic wall.
28
Define thrombosis.
Formation of a solid mass from blood constituents in an intact vessel in the living.
29
Give 2 reasons why thrombosis formation is uncommon.
1. Laminar flow.
| 2. Non sticky endothelial cells.
30
What are the 3 factors that can lead to thrombosis formation?
1. Change in vessel wall. (endothelial injury)
2. Change in blood constituents. (platelet aggregation, thrombus formation or fibrin deposition)
3. Change in blood flow. (stasis of blood flow)
31
Define embolus.
A mass of material (often a thrombus) that is carried in the vascular system that is able to become lodged in a vessel and block it.
32
Define ischaemia.
Decreased blood flow to tissues w/o other complications
33
Define infarction.
Decreased blood flow with subsequent cell death.
34
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.
35
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.
36
What can happen if ischaemia is rectified?
Re-perfusion injury can occur due to the release of waste products.
37
What are the consequences of an arterial embolus?
An arterial embolus can go anywhere! The consequences could be stroke, MI, gangrene etc.
38
What are the consequences of a venous embolus?
An embolus in the venous system will go onto the vena cava and then through the pulmonary arteries and become lodged in the lungs causing a pulmonary embolism. This means there is decreased perfusion to the lungs.
39
Through which blood system would an embolus have travelled if it resulted in a pulmonary embolism?
Venous system.
40
What drug can be used to prevent Thrombosis?
Aspirin.
41
Define atherosclerosis.
Inflammatory process characterised by hardened fibrolipid plaques in the intima of a vessel wall.
42
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.
43
What are the 3 main constituents of an atheromatous plaque?
1. Lipids.
2. Fibrous tissue.
3. Lymphocytes.
44
Give 5 risk factors for atherosclerosis.
1. Cigarette smoking.
2. Hypertension.
3. Hyperlipidaemia.
4. Uncontrolled diabetes mellitus.
5. Lower socioeconomic status.
45
What can be done to prevent atherosclerosis?
Reduce risk factors and taking low dose aspirin regularly.
46
What is the primary cause of atherosclerosis?
Endothelial cell damage.
47
Why can cigarette smoking lead to atherosclerosis?
Cigarette smoking releases free radicals, nicotine and CO into the body. These all damage endothelial cells.
48
Why can hypertension lead to atherosclerosis?
A higher blood pressure means there is a greater force exerted onto the endothelial cells and this can lead to damage.
49
Define apoptosis.
Programmed cell death of a single cell.
50
What is the role of p53 protein?
p53 protein looks for DNA damage, if damage is present p53 switches on apoptosis.
51
What protein can switch on apoptosis if DNA damage is present?
p53 protein.
52
Activation of which family of protease enzymes can turn on apoptosis?
Caspases.
53
Activation of what receptor can activate caspase and therefore apoptosis?
FAS receptor.
54
Give an example of a disease where there is too much apoptosis.
HIV.
55
Define necrosis.
Unprogrammed death of a large number of cells due to an adverse event where cell death is not expected
56
Give 3 examples of events that can lead to necrosis.
1. Frost bite.
2. Avascular necrosis.
3. Infarction.
57
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.
58
Define hypertrophy.
Increase in the size of a tissue due to an increase in the size of constituent cells.
59
Define hyperplasia.
Increase in the size of a tissue due to an increase in the number of constituent cells.
60
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.
61
Define metaplasia.
A change in the differentiation of a cell from one fully differentiated cell type to another fully differentiated cell type.
62
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.
63
Define dysplasia.
Morphological changes seen in cells in the progression to becoming cancer. The cells become more 'jumbled up'.
64
Define acute inflammation.
Initial and short lived tissue reactions to injury.
65
Define chronic inflammation.
Subsequent and prolonged tissue reactions to injury.
66
What happens to a cell when the telomere gets too short?
It can no longer divide.
67
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.
68
Why can excision be used as a cure for basal cell carcinoma?
Because BCC doesn't metastasise.
69
Suggest a treatment that could be used for leukemia?
Chemotherapy. Leukemia is systemic, it circulates all around the body, therefore excision can't be used.
70
Define carcinoma.
Malignant tumour of epithelial tissue.
71
Give an example of 5 carcinoma's that can spread to bone.
1. Breast.
2. Kidney.
3. Lung.
4. Prostate.
5. Thyroid.
72
Give an example of a carcinoma that can spread to the axillary lymph nodes.
Breast carcinomas.
73
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.
74
Give an advantage and a disadvantage of conventional chemotherapy.
- Advantage: works well for treatment against fast dividing tumours e.g. lymphomas.
- Disadvantage: it is non selective for tumour cells, normal cells are hit too; this results in bad side effects such as diarrhoea and hair loss.
75
What kind of carcinomas would targeted chemotherapy be most effective against?
Slower dividing tumours e.g. lung, colon and breast.
76
What is the theory behind targeted chemotherapy?
It exploits the differences between cancer cells and normal cells; this means it is more effective and has less side effects.
77
What kind of drugs can be used in targeted chemotherapy?
Monoclonal antibodies (MAB) and small molecular inhibitors (SMI).
78
What is required for a tumour to invade through a basement membrane?
1. Proteases.
| 2. Cell motility.
79
What is required for a tumour to enter the blood stream (intravasation)?
1. Collagenases.
| 2. Cell motility.
80
What is required for a tumour to exit the blood stream (extravasation)?
1. Adhesion receptors.
2. Collagenases.
3. Cell motility.
81
Give 2 promoters of tumour angiogenesis.
1. Vascular endothelial growth factors.
| 2. Fibroblast growth factors.
82
Give 3 inhibitors of tumour angiogenesis.
1. Angiostatin.
2. Endostatin.
3. Vasculostatin.
83
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.
84
Give an example of a malignant tumour that often spreads to the lung.
Sarcoma (via venae cavae -> heart -> pulmonary arteries).
85
Give an example of carcinomas that can spread to the liver.
Colon, stomach and pancreatic carcinomas can spread to the liver via the portal vein.
86
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.
87
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.
88
What is the main source of histamine?
Mast cells; histamine is stored in granules in their cytoplasm.
89
What enzymatic cascade systems does plasma contain?
1. The complement system.
2. The kinin system.
3. The coagulation system.
4. The fibrinolytic system.
90
What is the role of tissue macrophages in acute inflammation?
They secrete chemical mediators that attract neutrophil polymorphs.
91
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.
92
What is the major role of neutrophil polymorphs in acute inflammation?
Phagocytosis!
93
Define carcinogenesis.
A multistep process in which a normal cell evolves into a cancerous cell via permanent genetic mutations
94
Give an example of a situation when transplacental exposure lead to an increase in cancer risk.
The daughters of mothers who had taken diethylstiboestrol for morning sickness had an increased risk of vaginal cancer.
95
What percentage of cancer risk is due to environmental factors?
85% environmental, 15% genetic.
96
Give 5 host factors that can affect cancer risk.
1. Race.
2. Diet.
3. Constitutional factors (gender, age).
4. Premalignant conditions.
5. Transplacental exposure.
97
Name the 5 different categories of carcinogens.
1. Viral.
2. Chemical.
3. Ionising and non-ionising radiation.
4. Hormones, parasites and mycotoxins.
5. Miscellaneous e.g. asbestos and metals.
98
What causes skin cancer?
Exposure to UV light.
99
Chemical carcinogens: what types of cancer do polycyclic aromatic hydrocarbons cause?
Lung cancer and skin cancer.
100
Chemical carcinogens: what can expose people to polycyclic aromatic hydrocarbons?
Smoking cigarettes and mineral oils.
101
Chemical carcinogens: what types of cancer do aromatic amines cause?
Bladder cancer.
102
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.
103
Chemical carcinogens: what type of cancer do nitrosamines cause?
Gut cancer.
104
Chemical carcinogens: what type of cancer do alkylating agents cause?
Leukaemia; the risk is small in humans.
105
Define neoplasm.
An autonomous, abnormal, persistent new growth that continues to grow after the stimuli that caused the growth is removed
106
What is a neoplasm composed of?
1. Neoplastic cells.
| 2. Stroma.
107
Describe neoplastic cells.
Neoplastic cells are derived from nucleated cells. They're usually monoclonal and their growth and synthetic activity is related to the parent cell.
108
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.
109
What is essential for neoplasm growth?
Angiogenesis.
110
What does a neoplasm release in order to initiate angiogenesis?
Vascular endothelial growth factors.
111
Why does necrosis often occur in the centre of a neoplasm?
The neoplasm grows quickly and outgrows its vascular supply.
112
What are the advantages of classifying neoplasms?
It helps to determine the appropriate treatment and prognosis.
113
What are the two ways in which neoplasms can be classified?
1. Behavioural classification.
| 2. Histogenetic classification.
114
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.
115
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.
116
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. circumscribed or encapsulsted
6. Necrosis and ulceration are rare due to slow growth.
7. Exophytic growth.
117
What are the consequences of benign neoplasms?
1. Pressure on adjacent structures.
2. Obstruction to flow.
3. Transformation into malignant neoplasms.
4. Anxiety.
5. Produce hormones
118
What are the 7 main features of malignant neoplasms.
1. INVASIVE! Defining feature of a malignant tumour
2. Metastases.
3. Rapid growth, high mitotic activity.
4. Little Resemblance to normal tissue.
5. Poorly defined border due to invasive nature.
6. Necrosis and ulceration are common.
7. Endophytic growth.
119
What are the consequences of malignant neoplasms?
Destroy surrounding tissue, blood loss due to ulceration, pain, anxiety and all the benign effects
120
Define carcinoma.
MALIGNANT EPITHELIAL NEOPLASM!
121
Define sarcoma.
Malignant connective tissue neoplasm.
122
What is a rhabdomyoma?
Benign striated muscle neoplasm.
123
What is an adenoma?
Benign tumour of glandular epithelium.
124
What is a papilloma?
A non-glandular benign tumour.
125
What is a leiomyoma?
A benign smooth muscle neoplasm.
126
What is a neuroma?
A benign neoplasm of nerves.
127
What is a liposarcoma?
A malignant neoplasm of adipose tissue.
128
What is an Osteoma?
Benign neoplasm of bone tissue
129
What is an angioma?
Benign connective tissue neoplasm of the vasculature
130
What is a chondrosarcoma?
A malignant neoplasm of cartilage.
131
What is a melanoma?
A malignant neoplasm of melanocytes.
132
What type of tissue is affected in a Lipocarcinoma?
TRICK QUESTION
Lipo is adipose tissue which is a connective tissue. carcinoma is a malignant neoplasm of epithelial tissue.
Sarcoma is a malignant neoplasm of connective tissue
133
What is a lymphoma?
A malignant neoplasm of lymphoid cells.
134
Give examples of omas that are not neoplasms
Granuloma
Mycetoma
Tuberculoma
135
What kind of cancer is:
Burkitts Lymphoma
Ewings Sarcoma
Grawitz Tumour
Kaposi's Sarcoma
Burkitts Lymphoma - Lymphoma
Ewings Sarcoma - Bone cancer
Grawitz Tumour - Renal cell carcinoma
Kaposi's Sarcoma - Angiosarcoma
136
What is a teratoma?
A neoplasm that arises from all 3 germ cells of an embryo
137
What are blastomas?
These are embryonal tumours that resemble foetal tissue.
138
What are APUDomas?
Neuroendocrine tumours
139
What is a mesothelioma?
A malignant neoplasm of mesothelial cells.
140
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.
141
What must the immune system do in order to be effective?
The immune system has to discriminate self from non-self.
142
Describe innate immunity.
Non-specific, instinctive, present from birth, first line of defence. It is focused around physical and chemical barriers and phagocytosis. No lymphocyte involvement.
143
Give examples of physical and chemical barriers used in innate immunity?
Skin, mucociliary escalator, gastric acid, hairs, lysozymes etc.
144
What is the function of lysozyme?
It destroys bacterial cell walls.
145
Describe adaptive immunity.
Acquired, Specific, requires lymphocytes. immunological memory.
| 1st response is slow to build up the memory but the second responses are quicker and larger
146
Give examples of 3 polymorphonuclear leukocytes.
1. Neutrophils.
2. Basophils.
3. Eosinophils.
147
Give examples of 3 mononuclear leukocytes.
1. Monocytes.
2. B lymphocytes.
3. T lymphocytes.
148
In which primary lymphoid tissue do T cells mature?
Thymus.
149
In which primary lymphoid tissue do B cells mature?
Bone marrow.
150
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.
151
What is the function of T helper 1 (CD4)?
It helps the immune response against intracellular pathogens. Secretes cytokines.
152
What is the function of T helper 2 (CD4)?
It helps produce antibodies against extracellular pathogens. Secretes cytokines.
153
What is the function of Cytotoxic T cell (CD8)?
It can kill cells directly by binding to antigens; they induce apoptosis.
154
What is the function of T reg (FoxP3)?
They regulate the immune response.
155
Which cells express MHC1?
Ubiquitously expressed by almost all mammalian cells and all nucleated cells express MHC1. e.g. a virus infected or cancer cell would express MHC1.
156
Which cells express MHC2?
Antigen presenting cells ONLY e.g. macrophages, B cells, dendritic cells.
157
Which MHC would an intracellular antigen (endogenous) lead to the expression of?
MHC1.
158
Which MHC would an extracellular antigen (exogenous) lead to the expression of?
MHC2.
159
What type of T cell binds to MCH1?
Cytotoxic T cells (CD8).
160
What type of T cells binds to MCH2?
Helper T cells (CD4).
161
What do B cells differentiate into?
Plasma cells. The plasma cells then produce antibodies.
162
What does a helper T cell bind to?
A T cell receptor which is bound to an antigen epitope which is bound to MHC2 on an APC.
163
Describe T cell Activation
Naive T cell with the TCR binds to the epitope of the antigen presented via MHC on the APC
Co stimulatory molecule CD28 binds to CD80/CD86 on the APC to allow for full activation of the T cell.
The T cell will release IL-2 which then rebinds to the T cell IL-2-R to initiate T cell differentiation via autocrine mechanism.
The T cell will divide into Th1 or TH2 depending on the IL-12 concentration present at the time of differentiation.
164
What determines if a CD4 T cell differentiates into a Th1 or Th2 subtype when activated?
The concentration of IL-12 present
High IL-12 = Th1
Low IL-12 = Th2
165
What cytokines are released from Th1 cells and Th2 cells
Th1 - IL2 and INFy
Th2 - IL-4, IL-5, IL-10
166
What is the function of a Th1 T cell
Th1 cells stimulate cellular immune response, activate NK cells and macrophages to increase the innate response
167
What is the function of a Th2 T cell
Stimulates the humoral immune response by promoting B cell proliferation and antibody production
168
Describe Th1 T cell activation
APC presents Ag with MHC II to a naive CD4 T cell
Stimulation with high levels of IL-12 activates CD4 T cells to Th1 cells
Th1 cells travel to secondary lymph tissues where they proliferate (clonal expansion and T memory cells)
Th1 recognises Ag on infected cells via TCR
Th1 secretes INFy to stop viral spread and activate macrophages
169
Which interleukin is secreted when a helper T cell is bound to a T cell receptor?
IL-2. This then binds to an IL-2 receptor on the T cell and produces a positive feedback mechanism leading to division and differentiation.
170
How many antibodies can each B cell make?
Each B cell can only make 1 type of antibody. This 1 antibody can only bind to 1 epitope.
171
What happens to B cells that recognise 'self'?
They are killed in bone marrow.
172
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-cell epitope -> cytokine secretion of IL-4 and IL-5 induces B-cell clonal expansion and differentiation into plasma cells and memory B cells respectively
173
Give 3 functions of antibodies.
1. Neutralise toxins.
2. Opsonisation.
3. Activate classical complement system.
174
Which immunoglobulin is found in breast milk and other secretions?
IgA.
175
What are the 2 most common immunoglobulins?
IgG and IgM.
176
Which region of an antibody binds antigens?
The fab region.
177
Which region of an antibody binds to B cells?
The Fc region.
178
Which interleukins stimulate class switching to IgA and IgE?
IgA = IL-4
IgE = IL-5
179
Name 5 types of cytokines.
1. Interferons.
2. Interleukins.
3. Colony stimulating factors.
4. Tumour necrosis factors.
5. Chemokines
180
What is the function of interferons?
Interferons produce antiviral proteins.
181
What is the function of interleukins?
Interleukins cause cell division and differentiation.
can be pro-inflammatory or anti-inflammatory
182
What is the function of colony stimulating factor (CSF)?
CSF causes division and differentiation of bone marrow stem cells.
183
What is the function of tumour necrosis factor (TNF)?
TNF mediates inflammation and cytotoxic reactions.
184
What is the function of chemokines?
Chemokines attract leukocytes to sites of infection.
185
Define inflammation
A series of reactions that brings cells and molecules of the immune system to sites of infection or damage
186
Give an overview of the inflammatory response
Stop bleeding (coagulation)
Acute Inflammation (leukocyte recruitment)
Kill pathogens, neutralise toxins and limit pathogen spread
clear pathogens/dead cells (phagocytosis)
proliferation of cells to repair damage
remove blood clot - remodel extracellullar matrix
re-establish normal structure/function of tissue.
187
Give examples of secondary lymphoid tissue.
The spleen, lymph nodes, mucosa associated lymphoid tissue - MALT.
188
Describe the process of phagocytosis.
1. Pathogen binds to neutrophil/macrophage.
2. Engulfment of pathogen.
3. Phagosome formation.
4. Lysosome fusion - phagolysosome.
5. Pathogen is destroyed.
189
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.
190
What is the role of NO in killing pathogens?
NO leads to vasodilation and increased extravasation. This means more neutrophils etc pass into the tissues to destroy pathogens.
191
Why can superoxides be used to destroy pathogens?
Superoxides can be converted to H2O2 and then to hydroxyl free radicals. Hydroxyl free radicals are highly reactive and can destroy pathogens.
192
What mechanisms or cells are involved in O2 independent killing?
Defensins, lysozyme, pH, TNF.
193
Where are complement system plasma proteins derived from?
The liver.
194
What are the 3 main modes of action of the complement system activation?
1. Direct Pathogen lysis.
2. Opsonitation - Increased phagocytosis.
3. Inflammation - Activation of leukocytes such as macrophages via chemotaxis
195
What activates the classical complement pathway?
Antibodies.
196
Briefly describe the classical complement pathway.
1. C1s cleaves C4 -> C4a and C4b.
2. C4b binds C2b forming C4b2b. C4b2b is a C3 convertase and is responsible for C3 -> C3a and C3b.
3. C4b2b binds C3b forming C4b2b3b.
4. C5,6,7,8 and 9 also bind and eventually you get MAC formation. MAC is a pore like channel in a membrane.
197
What compound prevents excessive activation of the classical complement pathway?
C1 inhibitor.
| - C1 inhibitor leads to a negative feedback loop.
198
What activates the lectin pathway?
Mannose binding protein.
199
What activates the alternative pathway?
Bacterial cell walls and endotoxin.
200
What are the 3 different pathways that make up the complement system?
1. Classical.
2. Lectin.
3. Alternative.
201
Briefly describe the alternative pathway.
1. C3 reacts slowly with H2O forming C3(H2O).
2. C3(H2O) binds factor B. This becomes a substrate for cleavage by factor D.
3. Factor B is split into Bb and Ba.
4. Bb sticks to C3(H2O) forming C3(H2O)Bb.
5. C3(H2O)Bb is a C3 convertase that cleaves C3 into C3b and C3a.
6. C3b then binds to pathogens and causes opsonisation for improved phagocytosis. Also leads to MAC formation.
202
What is the function of these complement proteins:
MAC
C3a and C5a
C3b
MAC - Lyse microbes directly
C3a /C5a - Chemotaxis
C3b - Opsonisation
203
Which complement plasma proteins have opsonic properties when bound to a pathogen?
C3b and C4b.
204
What is the function of MAC in a pathogens' membrane?
MAC is a leaky pore like channel. Ions and water pass through the channel and disrupt the intracellular microbe environment -> microbe lysis.
205
Which complement plasma proteins are pro-inflammatory and cause chemotaxis and activation of neutrophils and monocytes etc?
C3a and C5a.
206
What kind of immunity are PRR's and PAMP's associated with?
Innate immunity.
207
What are PRR's a receptor for?
PAMP's.
208
Name 3 receptors that make up the PRR family.
1. Toll-like receptors (TLR).
2. Nod-like receptors (NLR).
3. Rig-like receptors (RLR).
209
What is the main function of TLR's?
TLR's send signals to the nucleus to secrete cytokines and interferons. These signals initiate tissue repair. Enhanced TLR signalling = improved immune response.
210
What is the main function of NLR's?
NLR's detect intracellular microbial pathogens. They release cytokines and can cause apoptosis if the cell is infected.
211
What disease could be caused by a non-functioning mutation in NOD2?
Crohn's disease.
212
What is the main function of RLR's?
RLR's detect intracellular double stranded RNA. This triggers interferon production and so an antiviral response.
213
TLR's are adapted to recognise damaged molecules. What characteristic do these damaged molecules often have in common?
They are often hydrophobic.
214
What kind of TLR's can be used in vaccine adjuvants?
TLR4 agonists.
215
Give examples of diseases that can be causes by PRR's failing to recognise pathogens.
1. Atherosclerosis.
2. COPD.
3. Arthritis.
216
Give examples of 3 extracellular PRR.
1. Mannose receptors.
2. Scavenger receptors.
3. TLR's.
217
What is the function of mannose and scavenger extracellular receptors?
The induce pathogen engulfment.
218
Give an example of an intracellular PRR.
NLR.
219
Where are circulating PRR secreted from?
Epithelia, phagocytes and the liver. They can activate the complement cascade and induce phagocytosis.
220
What happens when a PAMP binds to a PRR?
The innate immune response and inflammatory response is triggered.
221
What is extravasation?
Leukocyte (WBC) migration across the endothelium.
222
What do macrophages at the tissues secrete to initiate extravasation?
TNF alpha.
223
Describe the process of extravasation.
1. Macrophages at tissues release TNF alpha.
2. The endothelium is stimulated to express adhesion molecules (eg. GAG) and to stimulate chemokines.
3. Neutrophils bind to adhesion molecules (ICAM-1); they roll, slow down and become stuck to the endothelium.
4. Neutrophils are activated by chemokines.
5. Neutrophils pass through the endothelium to the tissue to help fight infection.
224
What 2 compounds can act as C3 convertase?
1. C4b2b - produced in the classical and lectin pathways.
| 2. C3(H2O)Bb - produced in the alternative pathway.
225
What type of cancers results from transformations in the germ line?
Inheritable cancers (<10%).
226
What type of cancers results from transformations in somatic cells?
Non-inheritable cancers (>90%).
227
What factors can cause transformations in somatic cells?
Environmental factors e.g. UV, chemicals (smoking can cause lung cancer), pathogens (HPV can cause cervical cancer).
228
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.
229
What are the two types of tumour antigens and where are they found?
1. Tumour specific antigens; only found on tumour cells. Due to point mutations.
2. Tumour associated antigens; found on normal cells and over expressed on tumour cells.
230
What is cancer immunosurveillance?
When the immune system recognises and destroys transformed cells, this is an important host protection process.
231
What is cancer immunoediting?
When the immune system kills tumour cells changes are induced in the tumour, the tumour cells are 'edited' by natural selection. The tumour cells are then disguised from the immune system, they escape destruction and recurrence is possible.
232
What are the 3 E's of cancer immunoediting?
1. Elimination.
2. Equilibrium.
3. Escape.
233
Give an example of active cancer immunotherapy.
Vaccination e.g. killed tumour vaccine, purified tumour antigens, APC-based vaccines etc.
234
Give an example of passive cancer immunotherapy.
T cell transfer, anti-tumour antibodies.
235
Why is hypoxia a prominent feature of a lot of malignant tumours?
Malignant tumours grow rapidly and so outgrow their blood supply.
236
Give 3 reasons why hypoxic tumours have a poor prognosis for the patient.
1. Hypoxic tumours have growth factors for angiogenesis and so can receive nutrients for growth.
2. They suppress the immune system.
3. They are resistant to chemotherapy and radiotherapy.
237
Define Active immunity and give a natural and artificial example
The immunity which results from the production of antibodies by the immune system in response to the presence of an antigen.
Natural - body encounters a pathogen
Artificial - Vaccines, mimics,
238
Define passive immunity and give a natural and artificial example
the short-term immunity which results from the introduction of antibodies from another person or animal.
Natural - Maternal Igs passed onto baby through breast milk/ colostrum
Artificial - Antivenom / Ig injection from another organism
239
Give 3 advantages of active immunity.
1. Induces immunological memory.
2. Produces high affinity antibodies.
3. It produces a persistent protective response against pathogens.
240
Give 2 advantages of passive immunity.
1. Immediate effect.
| 2. Useful treatment for acute dangers e.g. snake venom.
241
Give 3 disadvantages of passive immunity.
1. Short term.
2. No immunological memory produced.
3. Reaction is possible.
242
Describe the first immune response to initial exposure.
1. Innate immune response.
2. IgM predominates.
3. Low affinity.
243
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.
244
What is the purpose of a vaccine and how do they work?
A form of artificial active immunity which usually requires 2 doses - a primer and then a booster.
They work by inducing an immune response to mimic a natural infection without being symptomatic.
This creates IgM and IgG Abs so that upon genuine exposure to the pathogen the body can fight it.
245
What are the different types of components used in vaccines?
Live attenuated - Genetically modified organism (eg. MMR)
Antigens
Toxins - Tetanus
CW constituents - Hep B
DNA/RNA - eg. COVID-19
246
Give 3 advantages of live vaccines.
1. Very effective, prolonged and comprehensive.
2. Immunological memory produced.
3. Often only 1 vaccine is needed.
247
Give 2 disadvantages of live vaccines.
1. Immunocompromised patients may become ill.
| 2. Vaccines often need to be refrigerated which can be a problem in remote areas.
248
Give 2 advantages of inactivated vaccines.
1. There is no risk of infection.
| 2. Storage is less critical.
249
Give 3 disadvantages of inactivated vaccines.
1. Inactivated vaccines tend to only activate the humoral response; there is a lack of T cell involvement.
2. The response is often weak.
3. Boosters are needed and so patient compliance may be poor.
250
What is the role of an adjuvant?
An adjuvant is a substance added to a vaccination to stimulate an immune response. They convince your immune system that you're infected.
251
What can be used as an adjuvant?
Toxoids, proteins, chemicals (aluminium salts) etc.
252
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.
253
Give 3 advantages of transplantation.
1. Improved quality of life.
2. Improves survival rates.
3. Cost effective.
254
Why are immunosuppressive agents needed to prevent rejection?
Transplanted organs are recognised as non self and therefore are seen as a threat. Graft v host disease; T-cells destroy graft cells.
255
On which chromosome are MHC proteins found?
Chromosome 6.
256
Describe the transplant cascade.
Donor -> organ preservation -> implantation -> re-perfusion -> organ function.
257
What are the main compounds involved in reperfusion injury?
Free radicals e.g. H2O2, O2-, OH-. They damage cell walls.
258
Define allorecognition.
The ability of an organism to distinguish its own tissues from those of another. Recognition of non-self antigens.
259
What are the consequences of transplant rejection?
Fibrosis and scarring.
260
Describe the immune responses to detection of graft antigens.
1. Innate immune response is activated.
2. T cell mediated cytotoxicity.
3. Ab mediated cytotoxicity.
4. Hypersensitivity.
5. Tolerance.
261
Give 6 ways of preventing transplant rejection?
1. Manage risk factors.
2. Tissue typing.
3. Cross match.
4. Immunosuppressive agents.
5. Sensitisation and desensitisation.
6. Tolerance.
262
Why is it important to get the balance right when using immunosuppressive agents?
Too much = infection.
| Too little = rejection.
263
What is involved in tissue typing?
1. Blood group matching.
| 2. HLA typing.
264
What is involved in cross matching?
Detecting anti HLA antibodies.
| Cell based assays and solid phase assays can be used.
265
Define tolerance with regards to transplant immunology.
Tolerance is the acquired modification to host immunity leading to drug free transplant survival with full immunocompetence.
266
Define xenotransplantation.
Transplantation of tissues from one species to another.
267
What is allergy?
An abnormal response to harmless foreign material.
268
What is atopy?
The tendency to develop allergies.
269
Which immunoglobulin is most commonly involved in allergic responses?
IgE.
270
Which cells are most commonly involved in allergic responses?
Mast cells! Also eosinophils and basophils.
271
What happens to IgE receptors when a 'threat' is identified?
The receptors cross-link.
272
Which cells express high affinity IgE receptors?
Mast cells, basophils and eosinophils.
273
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.
274
What is the main IgE receptor cell?
MAST CELLS!
275
Which compound causes blood vessel dilation and vascular leakage in an allergic response?
Histamine.
276
What is the role of cytokine release in an allergic response?
They induce a TH2 response.
277
Which cells and which immunoglobulin is commonly involved in anaphylaxis?
- Mast cells and basophils.
| - IgE.
278
Give examples of anaphylactic systemic effects.
- CV: vasodilation, lowered BP.
- Resp: bronchial SM contraction, mucus.
- Skin: rash, swelling.
- GI: pain, vomiting.
279
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).
280
Define Immune Tolerance
Physiological destruction of T/B cells that recognise self antigens.
Central tolerance - Thymic tolerance of T cells
Peripheral Tolerance - If T/B cells evade central tolerance then they can be destroyed by Tregs in secondary lymphoid organs.
281
Define Autoimmunity
Pathological response where the immune system recognises self antigens and attacks these tissues.
282
Give some examples of organ-specific autoimmune diseases
T1DM - Endocrine pancreas - Beta cells
MS - oligodendrocytes of CNS
Pernicious anaemia - parietal cells of stomach
Hashimotos Thyroiditis - Anti-TPO Abs
Graves Disease - TSH-R
Myasthenia Gravis - Ach-R Abs
283
Give some examples of non-specific organ autoimmune diseases
SLE - DNA:ANA
Autoimmune haemolytic anaemia - RBCs
immune thrombocytopenic purpura - Platelets
284
Which infection is most often seen in patients with hypogammaglobulinemia?
Streptococcus penumonia sinusitis.
285
Give 5 examples of PAMPs.
1. Lipopolysaccharides.
2. Endotoxins.
3. Bacterial flagellin.
4. Peptidoglycans.
5. dsRNA.
286
Which PRR responds to lipopolysaccharides?
TLR-4.
Responds to LPS on gram negative bacteria
287
Is production of interferons (anti-viral proteins) part of the elimination phase of complement activation?
No
288
Give 4 causes of acquired immunodeficiency.
1. Cancer.
2. HIV.
3. Having chemotherapy.
4. Taking immunosuppressants.
289
What signs and symptoms might a person with HIV present with?
Fever, weight loss, recurrent infections, respiratory infections, TB.
290
What immune system cells are affected in HIV?
There is CD4 deficiency and B cell defects too. The adaptive immunity is affected.
291
What is the name of the disease that is characterised by B cell deficiency?
Hypogammaglobulinaemia.
292
What infection is most commonly seen in patients with hypogammaglobulinaemia?
Streptococcus pneumonia.
293
Describe hyper IgM syndrome.
High numbers of IgM. IgM is non specific and has a low affinity. IgM is unable to class switch to more 'useful' immunoglobulins and so IgA, IgE and IgG numbers are low.
294
What are the consequences of complement deficiency?
Impaired opsonisation of encapsulated bacteria.
295
What is terminal complement deficiency and what are its consequences?
- Terminal complement deficiency is when there's a problem with C5-8 and so MAC isn't produced.
- The consequences of this are chronic Neisserial infections and recurrent meningitis.
296
What are the consequences of being deficient in C1 inhibitor?
Angioedema - facial swelling.
297
What are the consequences of being deficient in C1, 2 or 4?
Increased likelihood of autoimmune disease especially systemic lupus erythematosus.
298
What are the consequences of hyposplenism?
Reticuloendothelial function is decreased. This means the body has difficulty dealing with encapsulated bacteria e.g. streptococcus pneumonia.
299
What is thymic aplasia?
A deficiency in mature T cells.
300
How can immune function be assessed?
1. Looking at neutrophil numbers, morphology and flow cytometry.
2. Looking at B and T cell subsets, numbers and response to vaccines.
3. Genetic studies.
301
Give 3 examples of chronic inflammatory diseases.
1. Rheumatoid arthritis.
2. Crohn's disease.
3. TB.
302
Name 3 conventional therapies used in managing CID.
1. NSAIDs.
2. DMARDs.
3. Steroids.
303
What disease are DMARDs most commonly used in the management of?
Rheumatoid arthritis.
| DMARD - disease-modifying antirheumatic drug
304
How do NSAIDs work in relieving inflammation.
NSAIDs inhibit COX 1 and 2. COX 2 is needed for prostaglandin synthesis. Prostaglandins are responsible for inflammation and pain. Therefore NSAIDs reduce symptoms of inflammation and pain.
305
What is a disadvantage of long term NSAID use?
NSAIDs can cause gastric bleeding. They inhibit COX 1 which is needed for prostaglandin synthesis and prostaglandins are needed for gastric mucus production.
306
Give 2 advantages of biological agents in treating chronic inflammatory disease?
1. They're extremely specific.
| 2. A low dose is very effective.
307
Give 5 disadvantages of biological agents in treating chronic inflammatory disease?
1. They're very expensive.
2. There is a risk of contamination.
3. They're always injected.
4. They're immunosuppressive.
5. They need to be handled carefully to prevent denaturation.
308
What class of biological agent is often used in the treatment of rheumatoid arthritis when DMARDs fail?
TNF blockers - they bind to TNF to prevent it interacting with its receptors.
309
Name 3 TNF blockers.
1. Etanercept (TNF alpha specific).
2. Infliximab.
3. Adalimumab.
310
What compound is often combined with biological agents to make treatment cheaper?
Methotrexate.
311
Give a side effect of using TNF blockers.
Increased susceptibility to TB.
312
How do IL-6 blockers work?
IL-6 is an inflammatory cytokine. The biological agent binds to IL-6 so as to prevent it interacting with its receptor.
313
Name an IL-6 blocker.
Tocilizumab.
314
When are IL-6 blockers used?
They're used in the treatment of rheumatoid arthritis when TNF blockers fail.
315
What are the risks of using IL-6 blockers?
They dampen the immune response and so you have an increased risk of infection. There is also an incerased risk of shingles and chickenpox.
316
Name 4 classes of biological agents and give an example of a drug for each.
1. TNF blockers e.g. etanercept.
2. IL-6 blockers e.g. Tocilizumab.
3. Anti B lymphocytes e.g. rituximab.
4. T cell activation blockers e.g. abatacept.
317
In what region of the antibody is there reversible bonding between antibodies and antigens?
Complementarity determining region (CDR).
| - Hydrogen bonds and VDW's etc form cumulative weak interactions that together form a strong force.
318
True or False. The heavy and light chains of an antibody are coded for by the same gene.
False. Distinct sets of genes code for the heavy and light chains.
319
What region determines Ig class?
The constant region!
320
What is the result of recombination in the Ig region?
Class switching.
321
Describe complement fixation.
An antibody binds multiple antigens so as to bring the Fc regions together. The complement pathway is initiated in this process and you get MAC formation.
322
Which compound is responsible for signalling when an antigen binds to an antibody?
Tyrosine kinase.
323
What immunoglobulin do naive antibodies express?
IgM.
324
Describe the process of class switching.
Antigen engagement and T cell help will result in class switching. A different FC region is used and there is affinity maturation.
325
What do T cells recognise?
PEPTIDES
326
Describe somatic hypermutation.
1. Random mutations in CDR.
2. Amino acid sequences are effected meaning Ab-Ag affinity is altered.
3. High affinity B cell clones are selected via natural selection.
327
Briefly describe the steps involved between T cell stimulation and plasma cell differentiation.
1. T cells are stimulated.
2. Cytokine release.
3. B cell proliferation.
4. Somatic hypermutation.
5. High affinity B cell clones differentiate into plasma cells and memory cells.
328
Give 4 uses of antibodies in medicine.
1. Diagnostic tools.
2. Immunoassays, Ab's are used to measure the presence of a molecule.
3. Flow cytometry, Ab's label cells in suspension.
4. Therapeutic uses, monoclonal Ab's can act as specific antagonists for biological targets e.g. HERCEPTIN.
329
Give an example of a proton pump inhibitor.
Omeprazole.
330
Give an example of a statin.
Simvastatin.
331
Give an example of an ACE inhibitor.
Enalapril.
332
Give an example of a COX inhibitor.
Aspirin and ibuprofen.
333
Give an example of a β2 adrenoceptor agonist.
Salbutamol.
334
Give an example of a β1 adrenoceptor blocker.
Atenolol.
335
Give an example of a Ca2+ channel blocker.
Amlodipine.
336
Give an example of a broad spectrum antibiotic.
Amoxicillin.
337
Give an example of an opiate analgesic.
Tramadol.
338
What do most drugs target?
Proteins!
339
Name 4 receptors that drugs target.
1. Ligand gated ion channels.
2. GPCR.
3. Kinase linked.
4. Cytosolic/nuclear.
340
Give an example of a ligand gated ion channel.
Nicotinic Ach receptor.
341
Give an example of a GPCR.
Muscarinic and β2 adrenoceptor.
| GPCR's usually interact with adenylate cyclase or phospholipase C
342
Give an example of a kinase linked receptor.
Receptors for growth factors.
343
Give an example of a cytosolic/nuclear receptor.
Steroid receptors; steroids affect transcription.
344
What are agonists?
Agonists bind to a receptor and to activate it.
345
What are antagonists?
Antagonists decrease the effect of an agonist. They show no response at a receptor.
346
Describe the shape of a log dose-response curve.
Sigmoidal.
347
What does EC50 tell us about a drug?
Its potency!
348
What is EC50?
The concentration of a drug that gives half the maximal response.
349
Would a drug with a lower EC50 have a lower or greater potency?
Greater potency.
350
What does Emax tell us about a drug?
Efficacy - it is the maximum response achievable.
351
What is the Intrinsic Activity of a drug?
The ability of a drug receptor complex to produce a maximum functional response
352
How can you calculate the intrinsic activity?
Emax of partial agonist / Emax of full agonist
353
Which is more efficacious, a full agonist or partial agonist?
A full agonist is more efficacious because a full agonist can give a 100% response.
354
Would an antagonist shift a dose-response curve to the left or right?
The antagonist would shift the dose-response curve to the RHS. The drug therefore becomes less potent.
355
Drug action: define affinity.
How well a ligand binds to a receptor.
356
Drug action: define efficacy.
How well a ligand activates a receptor; how well it induces a conformational change and how much of a response is achieved
357
What is the effect of fewer receptors on drug potency?
Fewer receptors will shift the dose-response curve to the RHS, this means drug potency will be reduced.
358
What is the effect of fewer receptors on receptor response?
Receptor response is still 100% due to receptor reserve. (Partial agonists don't have receptor reserve).
359
What is the affect of less signal amplification on drug response?
Less signal amplification gives a reduced drug response.
360
Describe allosteric modulation.
An allosteric modulator binds to a different site on a receptor and influences the role of an agonist.
361
What factors govern drug action?
Receptor related:
Affinity
Efficacy
Tissue Related:
Receptor number
Signal amplification
362
Define specificity and sensitivity in pharmacology
Specificity - The measure of a receptor's ability to respond to a single ligand. (low specificity results in physiological responses not targeted or intended by the drug eg. side effects) the drug acts on a certain target (eg. adrenoceptors)
Sensitivity - the drug acts on a subtype of a specific target (eg. b1 adrenoceptors rather than all adrenoceptors)
363
What is inverse agonism?
Where an agonist has a negative effect at a receptor and produces an opposite to expected response
364
Does an antagonist show efficacy?
No. An antagonist has affinity but zero efficacy. An agonist however demonstrates affinity and efficacy.
365
Pharmacology: define tolerance.
A reduction in the effect of a drug overtime. This can be due to continuous use of repeatedly high concentrations.
366
What 3 ways can a receptor be desensitised?
1. Uncoupled (an agonist would be unable to interact with a GPCR).
2. Internalised (endocytosis, the receptor is taken into vesicles in the cell).
3. Degraded.
367
Can aspirin be described as a selective drug?
No. Aspirin is non-selective, it acts on COX1 and COX2.
368
What is the function of COX1 and COX2?
They cyclise and oxygenate arachidonic acid and produce prostaglandin H2.
369
What does prostaglandin H2 form when it interacts with synthases?
Prostanoids.
370
Define pro-drugs and give an example of one.
Drugs that need to be activated enzymatically e.g. ACE inhibitors, enalapril.
371
How do ACE inhibitors work?
Angiotensinogen is converted to angiotensin 1 via renin. Angiotensin 1 is then converted to angiotensin 2 via ACE. ACE inhibitors prevents angiotensin 1 binding and so you don't get angiotensin 2 formation.
(Angiotensin 2 is a vasoconstrictor and so ACEi can be used in the treatment of hypertension).
372
Give an example of a β lactam antibiotic.
Penicillin and amoxicillin.
373
How do β lactam antibiotics work?
The inhibit transpeptidase and so prevent bacterial cell wall synthesis.
374
How do diuretics work?
They inhibit 'synporters' in the loop of henle. This leads to increased H2O excretion and decreased salt reabsorption and so BP decreases.
375
Give an example of loop of henle diuretics.
- Furosemide, act on the ascending loop.
| - Thiazides, act on the distal tubule.
376
How can drugs be developed?
1. Serendipity, by chance. e.g. penicillin.
| 2. Rational drug design. e.g. propranolol.
377
Describe how rational drug design works.
Rational drug design is focused on developing an antagonist from an agonist. It looks at solubility, electrostatic charge and bulk.
378
How do you determine whether insulin is long or short acting?
Small changes in amino acid sequence will determine whether insulin is long or short lasting - RECOMBINANT PROTEIN!
379
Name 3 things that the chemical properties of a drug can influence?
1. Administration.
2. Distribution.
3. Elimination.
380
As the difference in concentration falls what happens to the rate of reaction?
The rate of reaction will slow down.
| Rate is proportional to the concentration of drug
381
What is the association between diffusion and concentration gradient?
Diffusion is proportional to concentration gradient; this is a first order process and represents an exponential function.
382
How many litres of water are there in the following body compartments:
a) Plasma.
b) Interstitial space.
c) Intracellular space.
a) 3L.
b) 11L.
c) 28L.
383
What are the 5 ways by which fluid can move between compartments?
1. Simple diffusion.
2. Facilitated diffusion.
3. Active transport.
4. Movement through extra-cellular spaces.
5. Non-ionic diffusion.
384
What can influence the degree of ionisation of weak acids and weak bases?
pH.
385
What equation can be used to determine the degree of ionisation at a specific pH?
Henderson Hasselbach.
| pH = log[A-]/[HA] + pKa.
386
What can enhance non ionic diffusion?
Non ionic diffusion can be enhanced if adjacent compartments have pH difference.
387
In terms of ionisation, what happens to Aspirin in the stomach?
Aspirin is a weak acid and so becomes less ionised in the stomach due to the low gastric pH.
388
What is the advantage of aspirin becoming less ionised in the stomach?
This allows rapid non-ionic diffusion across the gut membrane into the plasma. Once in the plasma aspirin becomes more ionised again.
389
What is the effect of an increase in pH on a weak acid?
The weak acid will become more ionised.
390
What is the effect of an increase in pH on a weak base?
The weak base will become less ionised.
391
What is the effect of a decrease in pH on a weak acid?
The weak acid will become less ionised.
392
What is the effect of a decrease in pH on a weak base?
The weak base will become more ionised.
393
Define bioavailability.
The amount of drug taken up as a proportion of the amount administered. It is a reflection of uptake.
394
What route of drug administration has a bioavailability of 1?
IV infusion, all the drug administered will go into the plasma.
395
Explain what would happen to the bioavailability of aspirin if gastric pH increased.
The bioavailability would decrease. Aspirin would be more ionised and so wouldn't diffuse across the gut into the plasma as rapidly this would mean aspirin uptake would decrease.
396
Give 2 factors that drug distribution in the plasma depends upon.
1. Chemical properties.
| 2. Molecular size.
397
Write an equation for the volume of distribution (Vd).
Vd = amount of drug administered/concentration of drug in plasma.
398
If a drug had a high Vd what would that tell us about the drug?
This would indicate that the drug was highly lipid soluble and that most of the drug had moved into the intracellular space, less was in the plasma.
399
What is the relationship between plasma concentration and Vd?
Plasma concentration is inversely proportional to Vd.
400
Give 3 factors that can increase gastric pH.
1. Ingesting alkaline foods.
2. Antacids.
3. Omeprazole (PPI).
401
Give the two definitions for clearance.
1. The volume of plasma from which a drug is completely removed per unit time.
2. The rate at which plasma drug is eliminated per unit plasma concentration.
402
Write an equation for renal clearance.
Renal clearance = Rate of appearance in urine / plasma concentration.
403
What are the two ways by which drugs can be eliminated in the kidneys?
1. Glomerular filtration.
| 2. Active secretion.
404
What are the possible dangers of kidney damage with regards to renal clearance?
Kidney damage results in decreased renal clearance and so there is danger of accumulation, over dosage and toxicity.
405
What compound do many lipid soluble drugs combine with to increase their hydrophilicity?
Glucuronic acid.
406
Define hepatic extraction ratio (HER).
The proportion of a drug removed by one passage through the liver.
407
What is the limiting factor when a drug has a high HER?
Hepatic blood flow, perfusion limited.
408
What is the limiting factor when a drug has a low HER?
Diffusion limited. A low HER is slow and not efficient.
409
What happens to high and low HER drugs when enzyme induction is increased?
The clearance of low HER drugs increases. There is minimal effect on high HER drugs.
410
Where do phase 1 hepatic metabolism reactions occur?
In the smooth endoplasmic reticulum.
411
What enzyme usually catalyses phase 1 reactions?
CYP450.
412
What is a phase 2 hepatic metabolism reaction?
Phase 2 reactions involve conjugation and glucuronidation etc.
They usually inactivate products and increase hydrophilicity for renal excretion.
413
Give 3 advantages of IV infusion.
1. Steady state plasma levels are maintained.
2. Highly accurate drug delivery.
3. IV infusion can be used for drugs that would be ineffective when administered via an alternative route.
414
Give 3 disadvantages of IV infusion.
1. Expensive.
2. Needs constant checking.
3. Calculation error likely.
415
Give an advantage of a drug having a low Vd.
It is easy to reach steady state and plasma concentration is ‘responsive’ to dose rate.
416
Give 4 properties of the 'ideal drug'.
1. Small Vd (high bioavailability)
2. Drug broken down effectively by enzymes.
3. Predictable dose:response relationship.
4. Low risk of toxicity.
417
What are the advantages of pulsatile secretion as opposed to steady state?
1. Enhanced responsiveness.
| 2. More information can be conveyed.
418
What is the principal neurotransmitter in the body?
Acetylcholine.
419
What receptor does Ach interact within the somatic nervous system and the Symp and P.symp divisions of the autonomic nervous system?
Pre-synaptic neurone all ahve nicotinic ACh-Rs
Post-synaptic nicotinic receptors at the neuromuscular junction. in Somatic and Sympathetic NS.
Post - synaptic muscarinic receptor in the parasympathetic NS.
420
What type of receptor are nicotinic receptors?
Ligand gated ion channels.
421
Briefly describe how Ach is synthesised.
Acetyl CoA, choline and choline acetyl trasnferase combine to form acetylcholine. Ach is taken up into a vesicle in the presynpatic cleft and will be released following Ca2+ influx.
422
What enzyme is responsible for acetylcholine breakdown in the synaptic cleft?
Acetylcholinesterase.
423
Describe the action of botulinum toxin at the NMJ,
Botulinum toxin inhibits Ach release at the NMJ. Protease degrade vesicle proteins.
424
Describe the action of competitive antagonists at the NMJ.
They block Ach receptors. Competitive antagonists are muscle relaxants, adjuncts to general anaesthesia.
425
Describe the action of depolarising agonists (blockers) at the NMJ.
Depolarising agonists cause receptor desensitisation.
426
Describe the action of anticholinesterase inhibitors at the NMJ and give some examples of drugs.
There is increased Ach in the synaptic cleft. Ach can then compete with depolarising blockers.
neostigmine, rivastigmine
427
What type of receptor are muscarinic receptors? give some examples and where they function.
GPCR.
M1 - Brain
M2 - heart
M3 - lungs
428
Give examples of adverse muscarinic agonist effects.
1. Diarrhoea.
2. Urination.
3. Miosis.
4. Brachycardia.
5. Emesis (vomiting).
6. Lacrimation.
7. Salivation.
429
What happens in cholinergic crisis?
Overstimulation of Ach at NMJ results in SLUDGE
Salivation
Lactimation
Urination
Defaecation
GI distress
Emesis
430
Give 2 examples of Ach action in the CNS.
1. Motion sickness; Ach stimulates the vomiting centre in the brain.
2. Ach leads to increase dopamine re-uptake and so can worsen the symptoms of Parkinson's.
431
Briefly describe catecholamine synthesis.
Tyrosine -> L-DOPA -> Dopamine -> Noradrenaline -> Adrenaline.
432
Where does the conversion from Dopamine to Noradrenaline happen?
In a vesicle in the pre-synpatic neurone.
433
Which enzymes inactivate catecholamines?
MAO and COMPT.
434
Which protein does α1 interact with to activate phospholipase C?
Gq.
435
What is the primary function of α1 adrenoceptors and where are they commonly found?
Found on vessels and sphincters
α1 leads to vasoconstriction and bladder contraction and pupil dilation.
436
Which protein does α2 interact at the GPCR subunit ?
Gi.
437
What is the primary function of α2 and where are they found?
Mainly found in the CNS
α2 is responsible for pre-synaptic inhibition; it inhibits NAd release and result in sedation, analgesia.
438
What protein does β1,2,3 interact with in order to activate adenylate cyclase?
Gs.
439
What is the role of adenylate cyclase?
It converts ATP to cyclic AMP, this then leads to PKA synthesis.
440
What are the primary functions of β1 and where are they found?
Heart and kidneys
1. Increased cardiac effects e.g. force, rate and conduction. (ionotropic and chronotropic)
2. Increased renin secretion.
441
What are the primary functions of β2 and where are they found?
Lungs
1. Bronchodilation.
| 2. Vasodilation.
442
What are the primary functions of β3?
1. Increase lipolysis.
| 2. Bladder relaxation.
443
What would an α1 adrenergic antagonist do?
1. Vasodilation.
| 2. Relaxation of bladder neck = reduced resistance to bladder outflow.
444
What disease could an α1 adrenergic antagonist be used in the treatment of?
Hypertension
Symptomatic benign prostatic hypertrophy
445
What would a β1 adrenergic antagonist do? (beta blockers)
1. Reduce CO.
used in hypertension, tachycardia
| 2. Reduce renin secretion.
446
What diseases could an β1 adrenergic antagonist be used in the treatment of?
Hypertension, angina and arrhythmia, tachycardia.
447
What would a b2 antagonist cause?
bronchoconstriction
448
Give an example of a drug that is a b1 agonist and a disease that it could be used to treat.
Dobutamine
Cardiogenic shock
449
Give an example of a cardio-selective beta blocker and a nonselective beta blocker.
Atenolol/metoprolol
Propanolol/labetalol.
450
Define pain.
An unpleasant sensory and emotional experience associated with actual or potential tissue damage.
451
Give 3 advantages of pain.
1. Gives a warning for tissue damage.
2. Immobilisation for healing.
3. Memory establishment.
452
Define acute pain.
Pain caused by nociceptor activation. It is of short duration,
453
Define chronic pain.
Pain that is on-going or persistent, it lasts for >3-6 months.
454
Define neuropathic pain.
Pain caused by a primary lesion or dysfunction of the nervous system.
455
Define nociceptive pain.
Pain caused by actual or potential damage to non neural tissue, it is due to nociceptor activation.
456
Are A delta fibres myelinated or unmyelinated?
Myelinated.
457
Are C fibres myelinated or unmyelinated?
Unmyelinated.
458
Describe the type of pain that A delta fibres conveys.
Quick, sharp, localised.
459
Describe the type of pain that C fibres conveys.
Slow, dull, spread out.
460
Describe pain wind up.
A perceived increase in pain intensity over time when a stimulus is repeatedly delivered. It is caused by C fibre stimulation.
461
Describe the gate control theory.
Non-noxious stimuli trigger larger A beta fibres, these override smaller pain fibres and 'close the gate' to pain transmissions to the CNS.
462
What is pain treatment focused on?
1. Reducing excitatory neurotransmitters and nerve excitation.
2. Enhancing inhibitory neurones.
463
What are released in the presence of pain?
Endorphines.
464
What is an adverse drug reaction?
A noxious and unintended response to a drug.
Remember ABCDEs
465
Rawlins-Thompson system: Describe a type A adverse drug reaction.
- Augmented.
- Very common.
- Predictable from physiological effects of the drug.
- Often dose related.
466
Rawlins-Thompson system: Describe a type B adverse drug reaction.
- Bizarre.
- Unpredictable.
- Immunological mechanisms and hypersensitivity.
- Often there is a history of allergy.
467
Rawlins-Thompson system: Describe a type C adverse drug reaction.
- Chronic.
| - Occurs after long term therapy.
468
Rawlins-Thompson system: Describe a type D adverse drug reaction.
- Delayed.
| - Occurs many years after treatment.
469
Rawlins-Thompson system: Describe a type E adverse drug reaction.
- End of use.
| - Withdrawal reaction after long term use; complications of stopping medication.
470
What is the treatment for a type A adverse drug reaction?
Reduce the dose.
471
What is the treatment for a type B adverse drug reaction?
Withdraw drug immediately!
472
Describe type 1 hypersensitivity and give an example of a condition that causes this reaction.
IgE mediated hypersensitivity. Acute anaphylaxis. IgE becomes attached to mast cells upon first exposure. Second Exposure you get IgE cross linking leads to mast cell degranulation -> histamine.
Atopy - athsma, pollen, fur
473
Describe type 2 hypersensitivity and give an example of a condition that causes this reaction.
Antibody dependant cytotoxicity.
IgG/IgM mediated cytotoxicity by activating MAC complement when Ab binds to Ag. This incdes cell damage.
eg. Goodpastures syndrome, AIHA, Rheumatic Fever
474
Describe type 3 hypersensitivity and give an example of a condition that causes this reaction.
Immune complex deposition;
IgG/IgA bind antigen. activate complement.
immune complexes have not been adequately cleared by innate immune cells, giving rise to an inflammatory response.
eg. SLE, Post strep glomerulonephritits
475
Describe type 4 hypersensitivity and give an example of a condition that causes this reaction.
T cell-mediated.
Th1 activated by APC - initiates immune response
eg. DMT1, TB, MS, Guillian Barre
476
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.
477
What can cause a type 1 hypersensitivity reaction?
Pollen, cat hairs, peanuts etc. (allergies).
478
What can cause a type 2 hypersensitivity reaction?
Transplant rejection.
479
What can cause a type 3 hypersensitivity reaction?
Fungal.
480
What can cause a type 4 hypersensitivity reaction?
TB.
481
What is the treatment for anaphylaxis?
1. Commence basic life support (ABC).
2. Stop infusion of drug.
3. Give adrenaline Intramuscular 500mg and anti-histamines.
482
Give 4 risk factors for hypersensitivity.
1. Protein based macromolecules.
2. Female > male.
3. Immunosuppression.
4. Genetic factors.
483
Why are drug interactions such a big problem today?
1. Ageing population.
2. Polypharmacy.
3. Increased use of over the counter drugs.
484
Give 5 patient risk factors for drug interactions.
1. Old age.
2. Polypharmacy.
3. Renal disease.
4. Hepatic disease.
5. Genetics.
485
Give 3 drug related risk factors for drug interactions.
1. Narrow therapeutic index.
2. Steep dose/response curve.
3. Saturable metabolism.
486
Name 3 types of drug interaction.
1. Synergy; interaction of 2 compounds leads to a greater combined effect.
2. Antagonism; one drug blocks another.
3. Other.
487
How might drug interactions affect drug metabolism?
If a drug inhibits or induces CYP450 it might affect the metabolism of another drug.
488
How does avocado affect CYP450? And what drug might this impact on?
Avocado is a CYP450 inductor. Warfarin is likely to be affected and the risk of blood clots will be increased.
489
How does grapefruit juice affect CYP450? And what drugs might this impact on?
Grapefruit juice is a CYP450 inhibitor, it affects CYP3A4 specifically and increases the bioavailability of some drugs e.g. Ca2+ channel blockers and immunosuppressants.
490
Are weak acids cleared quicker if urine is more acidic or more alkali?
Weak acids are cleared quicker if urine is more alkali.
491
Are weak bases cleared quicker if urine is more acidic or more alkali?
Weak bases are cleared quicker if urine is more acidic.
492
What drug acts as an antagonist at the μ receptor?
Naloxone.
493
What enzyme is needed to metabolise codeine?
Codeine is a pro drug and needs to be metabolised by CYP2D6.
494
What is the bioavailability of morphine taken orally?
50%.
495
10mg of morphine is taken orally. What is the equivalent dose if given parenterally?
5mg.
496
What is morphine metabolised to?
Morphine 6 glucuronide.
497
Where might μ receptors be found?
In the epidural space and CSF.
498
Give 5 side effects of opioid use.
1. Respiratory depression.
2. Sedation.
3. Nausea.
4. Vomiting.
5. Constipation.
499
Describe the dose-response curve for morphine.
As dose increases response increases. This association is initially rapidly and then the graph plateaus. It is not sigmoidal!
500
Name a protein that can inhibit apoptosis.
BCL-2; it inhibits pro-apoptotic proteins e.g. caspase and therefore inhibits apoptosis.
501
What disease might develop in someone with a non-functional BCL-2 protein?
Cancer.
502
Where are mast cells found?
They are only found in tissues, not in the blood!
503
What is dobutamine used in the treatment of and at what receptor is it an agonist?
Dobutamine is a beta 1 agonist. It is used in the treatment of heart failure.
504
Define physiological antagonism.
A substance that produces effects that counteract the effects of another substance.
505
What are the 3 actions of NSAIDS?
1. Anti-inflammatory.
2. Analgesic.
3. Anti-pyrexic.
(AAA).
506
Name a local anaesthetic.
Lidocaine.
507
How do local anaesthetics work?
They inhibit pain by stopping impulse conduction in sensory nerves.
508
What drug inhibits ACh release at the NMJ?
Botulinum toxin.
| It is used to treat urinary incontinence and also cosmetically as a muscle relaxant.
509
Give 3 cytokines secreted by TH2.
1. IL-4.
2. IL-6.
3. IL-13.
4. IL-5.
5. IL-10.
510
What is the name of the variable region on an antibody?
Fab region.
511
Name 3 cytokines secreted by TH1.
1. IL-2.
2. Gamma-interferon.
3. TNF-beta.
512
Name 2 cytokines secreted by TREG.
1. IL-10.
| 2. TGF-beta.
513
Define adenocarcinoma.
A malignant neoplasm of glandular epithelium.
514
What is the initial reaction to tissue injury in inflammation?
Vessel lining becomes leaky (fluid exudate)
increased Permeability
mediator release (histamine and serotonin)
vessel dilation (plasma enters tissue w/clotting factors, nutrients, proteins and neutrophil polymorphs)
diagnostic presence
515
What is the microscopic appearance of chronic inflammation?
cellular infiltrate (lymphocytes, plasma cells, macrophages)
Granulation tissue becomes fibrous tissue
tissue damage and necrosis
516
What occurs during repair in chronic inflammation?
```
Angiogenesis
Fibroblast proliferation
Production of collagen
macrophages migrate
formation of granulation tissue
```
517
What is healing by 1st intention?
```
Incision
no loss of tissue
fibrinogen release
edges joined by fibrin (forms a clot)
replaced by collagen (little scar tissue)
structure and function restored
```
518
What is healing by 2nd intention?
```
Loss of tissue
Gap filled w/granulomatous tissue
adhesion of edges
organisation and fibrosis formation
leads to a big scar
```
519
What is inadequate wound healing?
```
Poor blood supply
poor nutrition
wound infection
immunosuppresion
diabetes
old age
```
520
What is excessive wound healing?
```
Hypertrophic scars
excessive collagen
stays within original wound site
keloid scars
Excessive granulation tissue that expands beyond wound edges
```
521
How does ageing affect the skin?
Wrinkling of skin (dermal elastosis) is caused by UV-B light causing crosslinking of proteins such as collagen in the dermis.
522
How does ageing affect the eyes
Cataracts are caused by UV-B cross linking of proteins in the lens causing opacity.
523
How does ageing affect the bones?
Osteoporosis - loss of bone matrix predominantly in women after menopause.
524
How does ageing affect the brain?
Dementia - Alzheimer's or vascular dementia.
| Can reduce likelihood of getting by reducing risk factors
525
How does ageing affect the muscle?
Loss of muscle (sarcopenia).
| Possible caused by reduced levels of GH and testosterone in later life.
526
How does ageing affect the ears?
Deafness - The hair cells in the cochlear do not divide so when they are damaged by high volumes they will die.
527
What is a basal cell carcinoma?
A skin cancer that is local and therefore will not metastasis
528
Define Congenital
Present at birth
| could be inherited or acquired
529
What are homeobox genes
control anatomical development
| when not expressed/mutated then defects occur
530
Give some examples of congenital abnormalities
Spina bifida 🡪 failure of closure of neural tube
Cleft lip 🡪failure of closure of palate
Ventricular septal defect 🡪 hole in ventricles
Syndactyly 🡪 webbing of toes & fingers via apoptosis
GH deficiency 🡪 decreased GH thus don’t grow
Acromegaly 🡪 increased HG post puberty so get big hands, feet & jaw [epiphyseal plates have been sealed]
Achondroplasia 🡪 mutation in fibroblast GF receptor gene thus long bones grow slower than the rest of the body
Growth impairment 🡪 mutation in type II collagen gene
531
Give some examples of inherited conditions
Chromosomal abnormality [3*Chr 21] 🡺 Downs syndrome
Autosomal dominant 🡺 Huntingtons disease
Autosomal recessive 🡺 Cystic fibrosis, Sickle cell
Sex linked 🡺 colour blindness
Co-dominant 🡺 blood groups
532
Define polygenic inheritance
Where a characteristic is controlled by 2+ genes
533
Define an inhertied condition
One that is caused by a genetic abnormalities inherited from parents
534
Define an acquired condition and give an example
Caused by non genetic environmental factors
eg. foetal alcohol syndrome
535
Define Tumour
Abnormal swelling
536
Define carcinogenesis
The evolution of a cancer cell from a normal cell via permanent genetic mutations
537
Define oncogenesis
Benign and malignant tumours
538
Define oncogenic
Tumour Causing
539
Define carcinogen
Cancer causing agents
540
Define carcinogenic
cancer causing
541
Define mutagenic
Acts of DNA
542
What tumours commonly metastasise to the lung
Sarcomas and any common cancer
543
What tumours commonly metastasise to the liver
```
Colomic
stomach
pancreas
carcinoid (tumours of the small intestine)
these all have portal venous drainage
```
544
What tumours commonly metastasise to the bone?
```
Prostate
breast
thyroid
lung
kidney
```
545
```
Which of the following tumours never metastasises
malignant melanoma
small cell carcinoma of the lung
basal cell carcinoma of the skin
breast cancer
```
Basal cell carcinoma
546
```
Which of these does not commonly metastasise to bone?
lung cancer
breast cancer
prostate cancer
liposarcoma
```
Liposarcoma
547
What term describes a cancer that has not invaded through the basement membrane?
Carcinoma in situ
548
what in the name of a benign tumour of glandular epithelium?
adenoma
549
What is the name of a malignant tumour of striated muscle?
Rhabdomyosarcoma
550
```
Which of these tumours does not have a screening programme in the UK?
Breast cancer
colorectal cancer
cervical cancer
lung cancer
```
Lung cancer
551
What is the name of a benign tumour of fat cells?
lipoma
552
What is the name of a malignant tumour of glandular epithelium?
Adenocarcinoma
553
What is the name of a malignant tumour of glandular epithelium?
Adenocarcinoma
554
What is the name of a malignant tumour of glandular epithelium?
Adenocarcinoma
555
What is another name for fibroids?
Leomyoma of the uterus
556
Give an example of a disease where there is a lack of apoptosis.
Cancer; mutations in p53 mean cell damage isn't detected.
557
Give examples of omas that are not neoplasms
Granuloma
Mycetoma
Tuberculoma
558
Difference between a viral and bacterial infection on appearance?
Viral infections often look red. Bacterial infections often have white pus alongside the red inflammation
559
How is inflammation classified?
Acute:
Sudden onset, short duration, usually resolves
Chronic:
Slow onset or sequel to acute
long duration
may never resolve
560
What cells are involved in inflammation?
neutrophil polymores
macrophages
lymphocytes
endothelial cells
fibroblasts
561
What is the function of neutrophil polymorphs?
Eat debris and bacteria
contain bags of enzymes (lysosomes) which are used to kill and digest phagocytosed bacterial
the first cells to arrive at the site of acute inflammation
562
What is the function of a macrophage?
phagocytose debris and bacteria,
transport material to lymph nodes and present this to lymphocytes to initiate a secondary immune reaction.
563
What are the functions of lymphocytes?
Produce chemicals involved in controlling inflammation and antibodies.
They are the immunological memory of the body.
564
What is the sequence of an acute inflammation?
Injury or infection
neutrophils arrive and phagocytose and release enzymes
macrophages arrive and phagocytose
either resolution with clearance of inflammation or progression to chronic inflammation
565
What is the sequence of Chronic Inflammation?
Progression from acute inflammation or starts as chronic inflammation
no or very few neutrophils
macrophages and lymphocytes and then fibroblasts
Can resolve if no tissue damage
often ends up with repair and formation of scars
566
What are granulomas
Particular type of chronic inflammation with collections of macrophages or histiocytes surrounded by lymphocytes
May be due to myobacterial infection such as TB or leprosy, chrons disease, sarcoidosis
567
What happens during repair?
replacement of damaged tissue by fibrous tissue
Collagen is produced by fibroblasts
568
What factors prevent the blood from clotting under normal circumstances?
Laminar Flow - cells travel in the centre of arterial vessels and do not touch the sides
Endothelial cells which line the vessels are not sticky when health
569
What is the time course of atherosclerosis throughout ages
Birth - no atherosclerosis
Late teenage/early 20s - fatty streaks in aorta which may not progress to established atherosclerosis
30s/40s/50s - development of established atherosclerotic plaques
40s to 80s - complications of atherosclerotic plaques including thrombosis, intraplaque haemorrhage
570
What is the major overall complication of atherosclerosis?
blocks an artery (via a superadded thrombosis or plaque haemorrhage) that prevents blood flow to its tissues that it supplies. This will result in infarction of that tissue.
571
Give examples of some specific atherosclerotic complications
Myocardial infarction
cerebral infarction
carotid atheroma
aortic aneurysms
peripheral vascular disease with intermittent claudication
gangrene
572
What controls the caspases involved in apoptosis?
Fas receptor and Fas ligand
Bcl2 family such as Bax (promotor) and Bcl2 (inhibitor)
573
Give some example of chemical carcinogens and the cacner they cause.
Polycyclic aromatic hydrocarbons - Lung and Skin
aromatic amines - Bladder
nitrosamines - Gut
alkylating agents - Leukaemia
574
Give some examples of DNA viruses that can cause cancer and their associated cancers
Human Herpes virus 8 - Kaposi Sarcoma
EBV - burkitt lymphom, nasopharyngeal carcinoma
HBV - HCC
HPV - SCC of cervix, penis, anus, head and neck
Merkle cell polyomavirus - merkle cell carcinoma
575
Give some examples of RNA viruses that can cause cancer
Human T lymphotrophic virus (HTLV-1) Adult T cell Leukaemia
HCV - HCC
576
What proportion of viral infections will result in cancer?
10-15%
577
Give some examples of biological agents that cause cancer
Hormones:
Oestrogen - increase mammary or endometrial cancer
Anabolic steroids - increase HCC risk
Mycotoxins:
Aflatoxin B1 - HCC
Parasites:
Chlonorchis sinesis - cholangiocarcinoma
Shistosoma - Bladder cancer
578
Give some examples of other miscellaneous carcinogens
Asbestos
Metals
579
Give some examples of premalignant conditions that can increase the risk of cancer
Colonic Polyps
Cervical Dysplasia
Ulcerative colitis
Undescended Testis
580
Give an exogenous and Endogenous ligand that activates TLR 1/2/6
Exo:
Gram positive lipopeptides
581
Give an exogenous and Endogenous ligand that activates TLR 3
Exo - dsDNA
Endo - mRNA
582
Give an exogenous and Endogenous ligand that activates TLR 4
Exo - LPS, pneumolysin, Viral Proteins
Endo - Heatshock proteins
583
Give an exogenous and Endogenous ligand that activates TLR 5
Exo - Flagellin
584
Give an exogenous and Endogenous ligand that activates TLR 7/8
Exo - ssRNA
585
Give an exogenous and Endogenous ligand that activates TLR 9
Exo - CpG DNA
Endo - DNA/mitochondrial DNA.
586
Define Synergism in pharmacology
Where 2 drugs with the same pharmacodynamic effect work together to provide an even greater effect than expected if you used the 2 drugs simultaneously.
(1 + 1 > 2)
587
Define summation in pharmacology
Where two drugs with the same pharmacodynamic effect work together to give an expected larger effect.
Eg. one drug reduces BP by 20mmHg and another reduces BP by 10mmHg. so together they reduce BP by 30mmHg
(1 + 1 = 2)
588
Define antagnoism in pharmacology
where two drugs will have contradicting effects. one may block another from working and so the overall net effect is 0
(1 + 1 = 0)
589
Define Potentiation in pharmacology
where one drug may increase the effect (potency) of another drug without affecting the effect of the first drug. (1 + 1 = 1 + 1.5)
590
What are the physiochemical effects of a drug?
The interactions that 2 drugs would have outside of the body due to their sole chemical properties.
591
Define Pharmacodynamics
The effects that a drug has on the body
592
Define Pharmacokinetics
What happens to the drug in the body
How the drug is ADME
Absorbed
Distributed
Metabolised
Excreted
593
Define Adsorption and give an example
Where a compound clings to the surface of another molecule
eg. In paracetamol overdose you could prescribe activated charcoal to stick to the paracetamol to prevent its absorption from the gut.
594
What is enzyme induction during the metabolism of a drug?
Where a drug may induce the CYP450 enzymes which can result in increased metabolism of a drug/prodrug to a more potent state and therefore potentially induce overdose.
595
WHat drugs may cause AKI?
NSAIDSs
ACEi
Furosemide
Gentimicin
596
What properties of a drug can affect its absorption
Motility - how fast it passes through the GI-Tract
Acidity - The ionised to un-ionised ratio
Solubility
pH Gradient - Affects the ionisation of a drug
597
What properties of a drug affect its distribution?
Whether it is soluble in plasma/tissues
Whether it is protein bound
598
What can affect how a drug is metabolised?
Phase 1 and phase 2 reactions in the liver
Enzyme induction (decrease therapeutic effect) or Enzyme inhibition (increase therapeutic effect) via CYP450s
599
What can affect how a drug is excreted?
Urine pH
Acids cleared faster if urine is weakly basic
Bases cleared faster if urine is weakly acidic
600
What is a receptor?
A component of a cell that interacts with a specific ligand and initiates a change of biochemical events leading to the ligands observed effects
601
What are the effects of a competitive antagonist?
Decreases potency of a drug but does not affect the efficacy
602
What are the effects of a non-competitive antagonist?
Decreases both the potency and efficacy.
603
Give an example of a selective and non-selective b-adrenergic agonist
Non-selective - Isoprenaline: activates both b1 and b2 receptors to increase heart muscle contractility and cause bronchodilation.
Selective - SAB2A: Selective b2 agonist and so will only cause bronchodilation.
604
Give an example of a cardio-selective beta blocker and a nonselective beta blocker.
Atenolol/metoprolol
Propanolol/labetalol.
605
What are the 5 types of Muscarinic Receptors?
M1 -Brain
M2 -Heart
M3- All organs with a parasympathetic innervation
M4 - Mainly CNS
M5 - Mainly CNS
606
What does activation of the M2 receptors on the SA and AV node do in the heart?
M2 at SA node - Decreases heart rate
M2 at AV node - decreases conduction velocity. Induces AV node block (increase PR interval)
607
What happens when M3 receptors are activated?
Parasympathetic effects of GI, Urinary system, eye
608
What is the only place in the body where the stimulation of M3 receptors causes a sympathetic response?
The skin - stimulation of M3 with ACh will cause sweating.
609
What is the use of Atropine?
Atropine is a muscarinic antagonist
Used intravenously to increase heart rate and treat brady arrythmias and AV node block
610
What is the used of inhaled antimuscarinics?
Used to result in airway bronchodilation by blocking the p.symp activation of bronchial smooth muscle.
611
What can some side effects of using anti-muscarinics be?
Inhibiting other M receptors and therefore causing dry mouth, urinary retention, worse glaucoma.
(stop other parasympathetic actions from working)
612
Give examples of drugs that will block the N1 receptor to inhibit ACh activity in the Somatic NS.
Rocuronium,
Suxamethonium
Pancuronium
all used as muscle relaxants in surgery.
613
Give examples of alpha 1 blockers and what they can be used to treat
Doxazosin - Decrease BP
Phenoxybenzamine - Treats phaeochromocytoma
614
What receptors are involved with the sympathetic and parasympathetic NS?
Sympathetic - Adrenergic receptors -alpha and beta
Parasympathetic - Cholinergic receptors - Nicotinic and Muscarinic
615
Define an adverse drug reaction
An unwanted or harmful reaction following the administration of a drug or combination of drugs under normal conditions of use and is suspected to be related to the drug.
It has to be noxious and unintended
616
What is the difference between a side effect and an adverse reaction?
Side effects are unintended effects but they can dome times be beneficial. An adverse reaction is never beneficial.
617
Define Toxic , collateral and Hyper-susceptibility effects
When ADRs occur:
Toxic - Beyond the therapeutic range
Collateral - Within Therapeutic Range
Hyper-Susceptibility effects - Below therapeutic range
618
Give examples of toxic effects of drugs
Nephrotoxicity
ototoxicity
dysarthria and ataxia
cerebellar signs and symptoms
619
What are some causes for ADRs (Adverse Drug Reactions)?
Pharmaceutical variation
receptor abnormality
abnormal biological system unmasked by the drug
abnormal drug metabolism
immunological effects
drug-drug interactions
multifactorial.
620
What is a Type F Drug reaction?
Failure of the drug to work.
Dose-related and is often caused by drug interactions either due to antagonism or enzyme induction/inhibition.
