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Pathology Flashcards

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1
Q

What is the role of the autopsy?

A

Who was the deceased?
When did they die?
Where did they die?
How did they come about their death?

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2
Q

What is the structure of an autopsy?

A
  1. History
  2. External examination
  3. Evisceration
  4. Internal examination
  5. Reconstruction
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3
Q

Name the three types of death referred to the coroner?

A

Presumed Natural (Cause not known
Presumed Iatrogenic
(Caused by care or surgery)
Presumed Unnatural

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4
Q

Define acute inflammation

A

Initial and transient series of tissue reactions to injury of short duration that normally resolves

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5
Q

Define chronic inflammation

A

Subsequent and prolonged tissue reactions following initial response (Sequel to acute that may never resolve)

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6
Q

What are the 5 cells involved in inflammation?

A 
Neutrophil polymorphs 
Macrophages 
Lymphocytes 
Endothelial cells 
Fibroblasts
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7
Q

Describe the roles of neutrophil in inflammation

A
  1. Short lived - first cells on scene
  2. Cytoplasmic granules full of bacteria killing enzymes
  3. Die at the scene of inflammation
  4. Release chemicals that attract other inflammatory cells (Macrophages)
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8
Q

Describe the role of macrophages in inflammation

A
  1. Long lived (Weeks to months)
  2. Phagocytic
  3. Ingest bacteria and debris
  4. May carry debris away
  5. Present antigens to lymphocytes
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9
Q

Describe the role of lymphocytes in inflammation

A
  1. long lived
  2. Produce chemicals that attract other inflammatory cells
  3. Immunological memory for past infections and antigens
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10
Q

Describe the role of endothelial cell in inflammation

A
  1. Line capillary blood vessels in areas of inflammation
  2. Become sticky in areas of inflammation so inflammatory cells adhere to them
  3. Become porous to allow inflammatory cells to pass into tissues
  4. Grow into areas of damage to form new capillary vessels
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11
Q

Describe the role of fibroblasts in inflammation

A

Long lived cells that form collagen in areas of chronic inflammation and repair

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12
Q

Name the 6 causes of acute inflammation

A
  1. Microbial Infections
  2. Hypersensitivity reactions
  3. Physical agents (Trauma, ionising radiation, heat and cold)
  4. Chemicals (Corrosive, acids, alkalis and reducing agents)
  5. Bacterial toxins
  6. Tissue necrosis
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13
Q

Define hypersensitivity Reactions

A

Reaction which occurs when an altered state of immunological responsiveness causes an inappropriate or excessive immune reaction that damages tissues

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14
Q

What are the 5 characteristic of acute inflammation

A
  1. Redness (Dilation of small blood vessels) Rubber
  2. Heat (Due to increased blood flow) Calor
  3. Swelling (oedema from accumulation of fluid in the extravascular space) Tumor
  4. Pain (Due to tissue distortion, pus under pressure in abscess cavity and chemical mediators that induce pain (Bradykinin, serotonin and prostaglandins) Dolor
  5. Loss of function
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15
Q

Name the three processes involved in the acute inflammatory response

A
  1. Change in vessel calibre (width) and increased flow
    - precapillary sphincters regulate flow through the capillary bed
  2. Increased vascular permeability and fluid exudate formation
  3. Formation of cellular exudate due to increased capillary hydrostatic pressure and escape of plasma proteins
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16
Q

Name the 4 outcomes of acute inflammation

A 
1. Resolution 
= complete restoration of tissue to normal 
2. Suppuration
= formation of pus 
3. Organisation
= tissue replaced by granulation tissue 
4. Progression to chronic inflammation
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17
Q

What are the 4 causes of chronic inflammation?

A
  1. Primary chronic inflammation
  2. Transplant rejection
  3. Progression from acute inflammation
  4. Recurrent episodes of acute inflammation
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18
Q

What are the features of chronic inflammation?

A
  • Cellular infiltrate consists of lymphocytes, plasma cells and macrophages
  • Macrophages may form multinucleate giant cells
  • Neutrophils are scarce
  • Continued tissue destruction - necrosis
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19
Q

What is a granuloma?

A

Aggregate of epithelioid histiocytes

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20
Q

Name some examples of granulomatous inflammation?

A
  1. Tuberculosis
  2. Leprosy
  3. Crohns disese
  4. Sarcoidosis
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21
Q

What causes histolytic giant cells to form?

A

Accumulation of particulate matter that is indigestible by macrophages

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22
Q

What do fibroblasts produce?

A

Collagen

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23
Q

Name 6 types of cell that are capable of regeneration

A 
Hepatocytes 
Pneumocytes 
All blood cells 
Gut epithelium 
Skin epithelium 
Osteocytes
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24
Q

Name 2 types of cell that do not regenerate

A

Myocardial cells

Neurones

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25
Define thrombus
Solid mass of blood constituents formed within an intact vascular system during life
26
Name 3 factors that pre-dispose thrombosis?
Change in the vessel wall = endothelial damage Change in the constituents of blood = more platelets Change in the blood flow = laminar to turbulent
27
Describe the formation of thrombus in veins
Slow blood flow in veins as not pulsatile so blood in stasis - if endothelial wall becomes sticky then thrombus forms but more slowly - most likely to form at valves
28
What are the 4 potential outcomes once a thrombus has formed
1. lysis and resolution 2. Organisation = scar tissue by invasion of macrophages which clear away the thrombus and fibroblasts and replane it with collagen 3. Recanalise = intimal cells of vessel on which the thrombus lies proliferate, capillaries grow through it and fuse to form larger vessels 4. Embolism = bit breaks off
29
Why does aspirin prevent thrombus formation
Because it is an anti platelet drug so prevents platelets binding to exposed collagen in endothelial wall and prevents further collagen aggregation
30
Define Embolus
Mass of material in the vascular system that is able to become lodged within a vessel and block its lumen
31
Define ischaemia
Reduction in blood flow
32
Define infarction
Death of cells due to reduced blood flow
33
Describe what happens in reperfusion injury
Limited blood supply has caused cells to become damaged but they have not died. If blood flow is restored to the cells then they may start to produce superoxide ions that cause damage to the cells
34
Are macrophages associated with acute or chronic infection?
Chronic
35
Are plasma cells associated with acute or chronic infection?
Chronic
36
Are neutrophil polymorphs associated with acute or chronic infection?
Acute
37
Are lymphocytes associated with acute or chronic infection
Chronic
38
Are giant cells associated with acute or chronic infection
Chronic
39
Define organisation
The repair of specialised tissues by the formation of a fibrous scar which forms due to the production of granulation tissue and removal of dead tissue by phagocytosis
40
What is granulation tissue made of?
Capillary loops and myofibroblasts
41
What is a granuloma
An aggregate of epithelioid histiocytes
42
Describe the process of repair
1. Capillary endothelial cells proliferate into the area forming a series of loops 2. Fibroblasts are stimulated and divide and secrete collagen 3. Fibroblasts acquire muscle filaments to form myofibroblasts 4. Capillary endothelial cells and the myofibroblasts = granulation tissue
43
Describe the process of healing by first intention
1. cut blood vessels either side are occluded by thrombosis and fibrin deposition binds the two sides 2. Coagulated blood on surface forms a scab to keep wound clean 3. Capillaries proliferate to bridge gap and fibroblasts secrete collagen 4. elastic network of dermis fails to reconnect 5. Basal epidermal cells proliferate over the gap
44
When does healing by second intention occur?
When there is tissue loss or the wound margins aren't apposed
45
Describe the characteristics of healing by second intention
1. Phagocytosis to remove debris 2. Granulation tissue to fill in the defects and repair specialised tissue 3. Epithelial regeneration to cover the surface
46
Describe the process of mucosal alteration
1. damaged mucosa replaced from margins 2. Damaged blood vessels bleed and surface becomes covered with fibrin layer 3. Macrophages remove dead tissue by phagocytosis 4. Granulation tissue produced in ulcer base as capillaries and myofibroblasts proliferate 5. Mucosa regenerates at margins and spreads across ulcer floor 6. Fibrous scar tissue replaces the muscle and distorts the stomach upon contraction
47
Define end artery
Tissues that only have one arterial supply and such if this is blocked there is no possibility of collateral supplies taking over
48
What two things determine whether ischaemia is reversible or not
1. Duration of the ischaemic period | 2. Metabolic demands of the tissue
49
Name the 5 macroscopic appearances of chronic inflammation
1. Chronic ulcer - breach of mucosa with a base lined by granulation tissue with fibrous tissue extending through the muscle layers of the wall 2. Chronic abscess cavity 3. Thickening of the wall of a hollow viscus by fibrous tissue 4. Granulomatous inflammation 5. Fibrosis
50
What do B lymphocytes become?
On contact with the antigen they become plasma cells
51
What do T lymphocytes become
1. On contact with antigen they produce cytokines which causes recruitment and activation of other cells 2. Responsible for cell mediated immunity
52
What is granulation tissue?
Important component of healing that comprises small blood vessels in a connective tissue matrix with myofibroblasts
53
What are the causes of chronic inflammation
Primary chronic inflammation Transplant rejection Progression/recurrent episode of acute inflammation
54
Define atherosclerosis
Disease characterised by the formation of elevated lesions in the intimal of large and medium sized arteries
55
What is the earliest lesion of an atherosclerotic plaque?
Fatty streak
56
What is a fatty streak?
Yellow linear elevation of the intimal lining composed of masses of lipid laden macrophages
57
Where do fatty streaks occur in the body?
In the systemic part of the body which is under higher pressure, not in the pulmonary part because these arteries are under low pressure
58
Where do atherosclerotic plaques form in the body?
Form at arterial branching points and bifurcations
59
What are the components of an atherosclerotic plaque?
``` Central lipid cholesterol core Fibrous tissue Collagen connective tissue cap Bordered by foam cells Lymphocytes (Chronic inflammation) Smooth muscle cells ```
60
What are the causes of atherosclerosis
``` Hypercholesterolaemia Smoking (Nicotine free radicals) Hypertension (Increased shearing forces) Diabetes (If poorly controlled) (Glucose damages endothelium) Hyperlipidaemia (Lipid damages endothelial cells) Low socioeconomic status] Male gender Increasing age ```
61
Describe the formation of an atherosclerotic plaque
1. Endothelial cell damage leading to increase expression of cell adhesion molecules and increased permeability to LDL 2. Inflammatory cells and lipids enter intimal layer and form plaques 3. Foam cells phagocytose LDL and die through apoptosis and spill their lipid content in enlarging lipid core 4. Plaques contains capillaries that can burst forming thrombi and haemorrhage causing plaque to increase in size
62
What are the complications of atherosclerosis?
Cerebral/myocardial infarct Abdominal aortic aneurysm leading to rupture or dilation Peripheral vascular disease --> Gangrene
63
Define apoptosis
Programmed cell death - defined sequence of intracellular events that lead to the removal of the cell without the release of products harmful to surrounding cells (enzymatic digestion of nuclear and cytoplasmic contents followed by phagocytosis of breakdown products)
64
What are the external signals that initiate apoptosis?
Detachment from extracellular matrix Withdrawal of growth factors Specific signals from other cells
65
What are the intracellular signals that initiate apoptosis?
DNA damage | Failure to conduct cell division
66
What are the characteristics of apoptosis?
1. Switch in cell determines time to die 2. Release internal enzymes that cause nucleus to shrivel, organelles moved to membrane bound vesicles 3. Macrophages eat this and no scar tissue remains
67
What causes DNA damage and triggers apoptosis?
cosmic rays and UV light
68
Which gene identifies DNA damage, induces cell cycle arrest and triggers the chemicals that switch on apoptosis
P53
69
What enzymes does p53 cause to be released to trigger apoptosis
Caspase
70
What is the affect of BCL2 on apoptosis?
Inhibiting caspases
71
What is the affect of Bax proteins on apoptosis?
Promote caspases
72
What is the affect of FAS ligand on apoptosis?
Stimulates caspases
73
Why is apoptosis important in development?
1. Interdigital cell death to separate fingers 2. Cell death to remove redundant tissue following palatine fusion during mouth of the roof development 3. Cell death to close the dorsal neural tube 4. Urachus cell death to remove redundant tissue between bladder and umbilicus
74
Define necrosis
Unintended cell death in response to cellular injury - traumatic process which induces inflammation and repair
75
Give 5 examples of necrosis
``` Toxic spider venom Frost bite Cerebral infarction Avascular necrosis of bone (Head of the femur and scaphoid) Pancreatitis ```
76
Define hypertrophy
Increase in the size of the tissue due to increases in the size of constituent cells
77
Define hyperplasia
Increase in the size of a tissue due to increases in the numbers of constituent cells
78
Give some examples of hyperplasia
Prostate Endometrial Endothelial Neuronal
79
When does a mix of hyperplasia and hypertrophy occur
In the uterus where the placental cells increase in size but also divide
80
Define atrophy
Decrease in the size of tissue caused by a decrease in the number of the constituent cells or a decrease in their size
81
Define metaplasia
Change in the differentiation of a cell from one fully differentiated type to a different fully differentiated type
82
Give two examples of metaplasia
Normally the lining of the bronchius is ciliated columnar epithelium but heavy smoking causes this epithelium to change to simple squamous Barrett's oesophagus - cells at the Lower end of the oesophagus change from stratified squamous epithelium to columnar
83
Define dysplasia
Imprecise term for morphological changes seen in the cells progression to becoming cancer
84
Why does the incidence of disease increase with age?
1. Probability of contact with an environmental cause increases with duration of exposure risk 2. Disease may depend on the cumulative effects of one or more environmental agent 3. Impaired immunity with ageing increases susceptibility to some infections 4. Latent interval between the exposure and appearance of symptoms may take decades
85
Define autosomal dominant
One copy of the gene is required for an individual to be affected
86
Define autosomal recessive
Both copies of the paired gene are required to be abnormal for expression of the disease
87
Define acquired disease
Caused by non genetic environmental factors ie. foetal alcohol syndrome
88
Name 5 mechanisms that cause cellular damage
Protein cross linking DNA cross linking DNA mutations that functionally alter the genes Mitochondrial damage Defects in oxygen and nutrient utilisation
89
What is the importance of telomeric shortening?
Telomere is non-coding region at end of chromosome - this sequence is not fully copied prior to mitosis As the cells divide the telomeres get shorter and shorter to the point the cell can no longer divide further
90
Name 6 age related conditions
1. Dermal elastosis - UVB hight causes collagen protein cross linking = wrinkles 2. Osteoporosis = loss of bone matrix due to lack of oestrogen increased resorption and decreased formation 3. Cataracts = UVB light crosslinks proteins making them opaque 4. Senile dementia - Brain atrophy 5. Sarcopenia = lack of muscle due to decreased growth hormone, decreased testosterone and increased catabolic cytokines 6. Deafness as the cilia in ears aren't replaced - loss of hair cells
91
What is the name of the main effector cell in acute inflammation
Neutrophil polymorph
92
What is the name of the cell that produces collagen in fibrous scarring?
Fibroblast
93
``` Which of the following is an example of acute inflammation Glandular fever Leprosy Appendicitis Tuberculosis ```
Appendicitis
94
What are the crystals deposited in joints in gout?
Uric acid
95
``` In which of the following does granulatomous inflammation occur? Crohns disease Acute appendicitis Infectious mononucleosis Lobar pneumonia ```
Crohns disease
96
What Is the specific name of calcification in diseased as opposed to normal tissues?
Stenosis
97
``` Which of the following is a chronic inflammatory process from its start? Appendicitis Cholecystitis Infectious mononucleosis Lobar Pneumonia ```
Infectious mononucleosis
98
What is the name given to cells that produce antibodies?
Plasma cells
99
What is the main cause of basal cell carcinoma?
Ultra violet light damaging the skin
100
What is the treatment for basal cell carcinoma and why is it the most appropriate option
Complete local excision because BCC only invades the skin locally
101
What is leukaemia?
Tumour of the WBC's so WBC circulate round the body and so will any tumours of the white blood cells
102
What are some of the symptoms of leukaemia?
``` Weight loss Fever Frequent infections Muscular weakness Pain and tenderness in the joints and bones Fatigue Loss of appetite Swelling of lymph nodes Enlarged spleen Night sweats Easy bleeding and bruising Purple patches or spots ```
103
What is the treatment for leukaemia?
Chemotherapy
104
Which cancers most commonly spread to the bone?
Breast, prostate, lung, thyroid and kidney
105
What is adjuvant therapy?
Extra treatment given after surgical resection
106
Name two ways to confirm a diagnosis of breast cancer?
Mammogram | Biopsy using core needle
107
How can you determine if breast cancer has spread to the axillary lymph nodes?
Ultrasound of the axilla
108
How can you check if breast cancer has spread to the rest of the body?
Bone and CT scan
109
What are the adjuvant therapies for breast cancer following lumpectomy?
Anti-oestrogen therapy Radiotherapy Herceptin
110
Define carcinogenesis
Transformation of normal cells to neoplastic cells through permanent genetic alterations or mutations
111
Define carcinogen
agents known or suspects to cause tumours by acting on DNA (Mutagenic)
112
What experimental evidence can be used to determine if something is a carcinogen?
Incidence of tumours in laboratory animals Cell/Tissue cultures Mutagenicity testing in bacterial cultures
113
What are the 5 classes of carcinogens?
1. Chemical 2. Viral 3. Ionising and non-ionising radiation 4. Biological agents = Hormones, parasites and mycotoxins 5. Miscellaneous
114
What sort of cancers is exposure to polycyclic aromatic hydrocarbons associated with?
Lung cancer | Skin cancer
115
What sort of cancer is exposure to aromatic amines associated with
Bladder cancer
116
What sort of cancer is exposure to nitrosamines associated with
Gut cancer
117
What sort of cancer is exposure to alkylating agents associated with?
Leukaemia
118
Increase exposure to UVA and UVB in ultraviolet light increases the risk of what conditions?
Basal cell carcinoma Melanoma Squamous cell carcinoma Xeroderma pigmentosum
119
Name three classes of biological agent that are carcinogens
Hormones Mycotoxins Parasites
120
Name 2 types of hormone that are considered carcinogens and the cancers they are associated with
Increased oestrogen = increased mammary/endometrial cancer | Anabolic steroids = hepatocellular carcinoma
121
Name a type of mycotoxin that is a carcinogen and what type of cancer it is associated with
Aflatoxin B1 --> Hepatocellular carcinoma
122
Name two types of parasites that are considered carcinogens and the cancers they are associated with
Chlonorchis sinensis --> Cholangiocarcinoma Shistosoma --> Bladder cancer
123
Name 2 types of miscellaneous carcinogens and the cancers they are associated with?
Asbestos = mesothelioma, asbestosis, lung cancer Metals
124
Name some host factors that may determine susceptibility to carcinogenesis
``` Race Diet Constitutional factors = Age, inherited predisposition, gender Premalignant lesions Transplacental exposure ```
125
Define tumour
Any abnormal swelling
126
Define Neoplasm
A lesion resulting from the autonomous or relatively autonomous abnormal growth of cells which persists after the initiating stimulus has been removed
127
Which processes initiate the formation of neoplasms
Accumulation of genetic alterations such as mutations, translocations, rearrangements, amplifications and epigenetic changes that enable the cell to escape normal growth regulatory mechanisms
128
What are the two main components of a neoplasm?
1. Neoplastic cells - synthesise and secrete collagen, mucin and keratin that accumulate in the tumour 2. Stroma
129
Where are neoplastic cells derived from
Monoclonal nucleated cells that have a growth pattern similar to the parent cell
130
Where is the purpose of the stroma component of a neoplasm?
mechanical support Intracellular signalling Nutrition to neoplastic cells
131
How is the stroma component of a neoplasm formed?
Connective tissue fibroblast proliferation by growth factors from the tumour cells
132
Which growth factor induces angiogenesis?
Vascular endothelial growth factor
133
What is the maximum size of a tumour before angiogenesis occurs and why is the case?
1-2mm because without blood vessels its supply of nutrients is limited due to the constraints of effective diffusion
134
What are the 6 types of tumour shape?
``` Sessile Polypoid Papillary Exophytic/fungating Ulcerate Annular ```
135
Give two reasons why we classify neoplasms?
To determine the appropriate treatment | To provide prognostic information
136
What are the two main ways of classifying neoplasms?
``` Behavioural = benign or malignant Histogenetic = cell of origin ```
137
What are the characteristics of a benign neoplasm?
``` Localised and non-invasive Slow growth rate Low mitotic activity Close resemblance to the normal tissue Encapsulated by thin layer of connective tissue Nuclear morphometry normal Necrosis rare Ulceration rare Growth of mucosal surfaces often exophytic (Upwards an outwards from surface) ```
138
Why should we worry about benign neoplasms?
1. Pressure on adjacent structures - lead to necrosis 2. Obstruct flow 3. Production of hormones (benign thyroid tumour causing thyrotoxicosis) 4. Transformation to malignant neoplasm 5. Anxiety to patient
139
What are the characteristics of a malignant tumour?
``` Invasive Metastases Rapid growth compared to benign Do not resemble the parent tissue as much as benign neoplasms do Poorly defined or irregular border Hyperchromatic nuclei Pleomorphic nuclei Increased mitotic activity necrosis common Ulceration common Growth on mucosal surfaces is endophytic (Inwards and downwards from surface) ```
140
Why should we worry about malignant neoplasms?
Destruction of adjacent tissues Metastases leading to formation of secondary tumours Blood loss from ulcerated surfaces Obstruction of blood flow Hormone production (ACTH and ADH) Paraneoplastic effects - symptoms not just due to cancer at that site (Weight loss) Anxiety and pain
141
Why do malignant tumours show central necrosis?
Inadequate perfusion
142
Define histogenesis?
Specific cell of origin of a tumour
143
What neoplasm arises from epithelial cells
Carcinomas
144
What neoplasm arises from connective tissues?
Sarcomas
145
What neoplasm arises from lymphoid/haemopoietic organs
Lymphomas
146
What is a papilloma?
A benign tumour of non-glandular, non-secretory epithelium such as squamous cell papilloma
147
What is an adenoma?
A benign tumour of glandular or secretory epithelium such as colonic adenoma
148
What is a carcinoma?
A malignant epithelial neoplasm of non-glandular epithelial cells ie. transitional cell carcinoma
149
What is an adenocarcinoma?
A malignant epithelial neoplasm of glandular epithelium such as adenocarcinoma of the breast or prostate
150
Name 7 types of benign connective tissue neoplasm?
1. Lipoma = adipocytes 2. Chondroma = cartilage 3. Osteoma = bone 4. Angioma = vascular 5. Rabdomyoma = striated muscle 6. Leiomyoma = Smooth muscle 7. Neuroma = benign neoplasm of nerves
151
Name 6 types of malignant connective tissue neoplasm
1. Liposarcoma = adipocytes 2. Rhabdomyosarcoma = striated muscle 3. Leiomyosarcoma = smooth muscle 4. Chondrosarcoma = cartilage 5. Osteosarcoma = bone 6. Angiosarcoma = blood vessels
152
What is a melanoma?
Malignant neoplasm of melanocytes
153
What is a mesothelioma?
Malignant tumour of mesothelial cells
154
What is a lymphoma?
Malignant neoplasm of lymphoid cells
155
What is Burkitts lymphoma
B-cell lymphoma associated with Epstein Barr virus
156
What is Ewings sarcoma?
Malignant tumour of the bone
157
What is Grawitz tumour?
Renal cell carcinoma
158
What is Kaposi sarcoma?
Malignant neoplasm derived from vascular endothelium commonly associated with AIDS
159
What are the three ways of grading a malignancy?
Low grade = looks like parent tissue High grade= doesn't look like parent tissue Anaplastic = unknown origin cell type
160
What is carcinoma in situ?
When the cancer divides quicker than the normal cells and doesn't apoptosis but is yet to invade
161
What enzymes are required for cancers to invade through the basement membrane
Matrix metalloproteinases Collagenases Cathepsin D Urokinase-type plasminogen activator
162
What is metastasis?
Metastasis is the process by which a malignant tumour spreads from its primary site of origin to produce secondary tumours at distant sites
163
What are the three factors influencing tumour invasion?
1. decreased cellular adhesion 2. Secretion of proteolytic enzymes 3. Abnormal or increased cellular motility
164
Describe the process of cancer cell metastasis
1. Detachment of tumour cells from their neighbours 2. Invasion of the surrounding connective tissue to reach conduits for metastasis (blood and lymphatic vessels) 3. Intravasation into the lumen of vessels 4. Evasion of host defence mechanism such as natural killers cells In the blood 5. Adherence to the endothelium at remote location 6. Extravasation of cells from the vessel lumen into the surrounding tissue
165
Name three ways in which cancer cells avoid the host immune defence
- Aggregate with platelets so body cant detect it - Shedding surface antigens so not recognised - Adhesion to other tumour cells – ‘safety in numbers’
166
Name two factors that promote angiogenesis
Vascular endothelial growth factor | Basic fibroblast growth factor
167
Name three factors that inhibit angiogenesis
Angiostatin Endostatin Vasculostatin
168
What are the three possible routes for metastasis?
Hamatogenous - bloodstream Lymphatic Transcoelomic - pleural, pericardial and peritoneal cavities
169
Where do sarcomas commonly metastasise to?
Lung
170
Where does colorectal cancer normaly end up
Liver
171
Where to tumours of the colon, stomach, pancreas, and intestine normally end up?
liver
172
Where do tumours of the prostate, breast, thyroid, lung and kidney normally metastasise to?
bone
173
Define inflammation
A local physiological response to tissue injury
174
Give a benefit of inflammation
Inflammation can destroy invading micro-organisms and can prevent the spread of infection
175
Give a disadvantage of inflammation
Inflammation can produce disease and can lead to distorted tissues with permanently altered function
176
Define exudate
A protein rich fluid that leaks out of vessel walls du to increased vascular permeability
177
What does viral infection result in?
Cell death due to intracellular multiplication
178
What does bacterial infection result in?
Release of exotoxins involved in initiation of inflammation or endotoxins
179
How can acute inflammation be diagnosed histologically?
By looking for the presence of neutrophil polymorphs
180
Give three endogenous chemical mediators of acute inflammation?
1. Bradykinin 2. Histamine 3. Nitric oxide
181
What are the 4 systemic effects of acute inflammation?
1. Fever 2. Feeling unwell 3. Weight loss 4. Reactive hyperplasia of reticuloendothelial system
182
What cells are involved in chronic inflammation
Macrophages and plasma cells (B and T lymphocytes)
183
What are 4 macroscopic features of chronic inflammation
1. chronic ulcer 2. Chronic abscess cavity 3. Granulomatous inflammation 4. Fibrosis
184
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
185
Give 2 reasons why thrombosis formation is uncommon?
1. Laminar flow | 2. Non-sticky endothelial cells
186
Why are tissues with an end arterial supply more susceptible to infarction
Because they have a single arterial supply and if this becomes interrupted then infarction is likely
187
Give three examples of organs with a dual arterial supply
1. Lungs (Bronchial and pulmonary veins 2. Liver hepatic arteries and portal veins 3. Some areas of the brain around the circle of Willis
188
What are the consequences of a venous embolus
Embolus in the venous system goes to vena can and through the pulmonary arteries becoming lodged in the lungs and causing a pulmonary embolism which decreases perfusion to the lungs
189
Give an example of a disease where there is a lack of apoptosis
Cancer, mutations In p53 mean cell damage isn't detected
190
Give an example of a disease where there is too much apoptosis
HIV
191
Give three differences between apoptosis and necrosis
1. Apoptosis is programmed cell death whereas necrosis is unprogrammed 2. Apoptosis tends to effect a single cell whereas necrosis affects a number of cells 3. Apoptosis is a response to DA damage whereas necrosis is triggered by an adverse event
192
Give three examples of events that can lead to necrosis
1. Frost bite 2. Avascular necrosis 3. Infarction
193
Why is adjuvant therapy often used in the treatment of carcinomas
Micrometastes are possible even if the tumour is excised so adjuvant therapy is given to suppress the secondary tumour formation
194
Give an advantage and disadvantage of conventional chemotherapy
Advantage = Works well for treatment against fast dividing tumours Disadvantage = non selective for tumour cells resulting in effects such as diarrhoea and hair losss
195
What type of carcinomas would be targeted chemotherapy be most effective against
Slower dividing tumours ie. lung, colon and breast
196
What is the theory behind targeted chemotherapy
It exploits the differences between cancer cells and normal cells
197
What kind of drugs can be used in targeted chemotherapy?
Monoclonal antibodies (MAB) and small molecular inhibitors (SMI)
198
What Is required for a tumour to invade through the basement membrane
1. Proteases | 2. Cell motility
199
What is required for a tumour to enter the blood stream (Intravasation)
1. Collagenases | 2. Cell motility
200
What is required for a tumour to exit the blood steam (extravasation)
1. Adhesion receptors 2. Collagenases 3. Cell motility
201
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 such as bradykinin and prostaglandins which induce pain
202
Define carcinogenesis
A multistep process in which normal cells become neoplastic cells due to mutations
203
What percentage of cancer risk is due to environmental factors?
85%
204
Give an example of a situation when transplacental exposure leads to an increase in cancer risk
Daughters of mothers who had taken diethylstilbestrol for morning sickness had an increased risk of vaginal cancer
205
Define carcinoma
Malignant epithelial neoplasm
206
Define sarcoma
Malignant connective tissue neoplasm
207
What are the 4 characteristics of innate immunity?
``` Instinctive Non-specific Does not depend on lymphocytes Present from birth Immediate, rapid response ```
208
What are the 3 characteristics of adaptive immunity?
Specific/Acquired immunity Requires lymphocytes and antibodies Slower response
209
What are the three observable layers when blood is centrifuged?
1. Upper plasma layer containing 90% water, electrolytes, proteins, lipids and sugars 2. Middle white fluffy layer containing lymphocytes 3. Lower layer (45%) containing erythrocytes and platelets
210
What is serum?
Plasma without fibrinogen and other clotting factors
211
Which cell is the cell of origin of immune cells
Multipotent Haemopoietic stem cell (Haemocytoblast)
212
Draw a diagram to show the origin of immune cells
Find diagram on internet
213
What chemical stimulates stem cells to differentiate into blood cells?
Cytokines
214
What are the three types of polymorphonuclear leukocytes
Neutrophil Eosinophil Basophil
215
What are the three types of mononuclear leukocytes and what do they become
Monocyte --> becomes macrophage when moves from blood to tissue T cell becomes T-Reg, T-Helper (CD4) or cytotoxic (CD8) B-cell becomes plasma cells when activated which become antibodies
216
What is complement
Group of 20 serum proteins secreted by the liver that need to be activated to be functional as part of the immune system
217
What are the three modes of action of the complement system?
1. Direct lysis (Membrane attack complex that makes a hole in pathogen) 2. Attract more leukocytes to the site of infection (Chemotaxis) 3. Coat invading organisms to make it more easy for them to be engulfed by phagocytic cells (Opsonisation)
218
what do antibodies bind to?
Antigens
219
What are the 5 classes of antibody?
``` IgG IgA IgM IgD IgE ```
220
Describe the properties of IgG
Most predominant in human 70-75% of antibodies Can get anywhere in the body Only Ig that can cross the placenta
221
Describe the properties IgA
Monomer Accounts for 15% in serum Predominant Ig in mucous secretions including milk, saliva, bronchiolar and genitourinary secretions
222
Describe the properties of IgM
Pentagon molecule Mainly resides in the blood serum because its so large Primary immune response Accounts for 10% of Ig in serum
223
Describe the properties of IgD
1% of serum | Expressed on naive B cells and acts as B-cell antigen receptor
224
Describe the properties of IgE
0.05% in serum Basophils and mast cells express IgE receptor so have high affinity for IgE IgE associated with hypersensitivity allergic reactions and defence against parasites binding antigen triggers release of histamine by basophils and mast cells
225
What are cytokines
Proteins secreted by immune and non-immune cells that acts as stimulatory or inhibitory signals between the cells
226
Give 4 examples of cytokines
Interferons Interleukins Colony stimulating factors Tumour necrosis factors
227
Describe the function of interferons and give two examples
Induce a state of antiviral resistance in unaffected cells and limit the spread of infection IFNa and IFNb IFNy
228
What cells produced IFNa and IFNb
Virus infected cells
229
What cells produce IFNy
Activated Th1 cells
230
What is the function of Interleukins?
Can produce a pro inflammatory (IL1) or anti-inflammatory (IL-10) response the can cause cells to divide, differentiate and secrete factors
231
What is the function of colony stimulating factor?
Involved in directing the division and differentiation on bone marrow stem cells - precursors to leukocytes
232
What is the function of tumour necrosis factor and give 2 examples
Mediate inflammation and cytoxic reactions | TNFa and TNFb
233
What are chemokines
Group of 40 proteins that direct the movement of leukocytes from the bloodstream into tissues or lymph by binding to specific receptors on cells
234
What are the 8 characteristics of the innate defence mechanism?
1. Non specific 2. 1st line of defence 3. Provides barrier to antigen 4. Instinctive 5. Present from birth 6. Slow response 7. No memory 8. Does not depend on immune recognition by lymphocytes
235
What are the 5 characteristics of the adaptive defence mechanism?
1. Specific 2. Response to a specific antigen 3. Learnt behaviour 4. Memory to specific antigen 5. Quicker response
236
What is the innate immunity composed of?
``` Physical and chemical barriers Phagocytic cells (Neutrophils and macrophages) Blood proteins (Complementt) ```
237
What are the physical barriers to infection?
1. Lysozymes in tears 2. Skin 3. Skin sebum secretions 3. Acidic pH in vagina 4. Acidic pH in gut 5. Removal of particles by passing air over turbinates bones 6. Mucus and cilia in bronchi
238
What are the 7 stages of the response to inflammation?
1. Stop bleeding 2. Acute inflammation (Leukocyte recruitment) 3. Kill pathogen, neutralise toxins and limit pathogen spread 4. Clear pathogens and dead cells (Phagocytosis) 5. Proliferation of cells to repair the damage 6. Remove blood clot and remodel the extracellular matrix 7. Re-establish normal structure and function of tissue
239
Define inflammation
Series of reactions that brings cells and molecules of the immune system to sites of infection or damage
240
What are three signs of inflammation
1. Increased blood supply 2. Increased vascular permeability 3. Increased leukocyte transendothelial migration
241
Define acute inflammation?
Complete elimination of a pathogen followed by resolution of damage, disappearance of leukocytes and full tissue regeneration
242
Define chronic inflammation?
Persistent unresolved inflammation
243
What senses microbes in the blood?
Monocytes and neutrophils
244
What senses microbes in the tissues?
macrophages and dendritic cells
245
Where are pattern recognition receptors found
On immune cells
246
Where are pathogen associated molecular patterns found
On the microbe
247
Describe the process of extravasation?
1. Microbe in tissue with macrophage bound 2. Macrophage secretes pro-inflmmatory TNFa 3. TNF interacts with endothelium making it sticky 4. Neutrophil sticks to endothelium and rolls along its surface 5. TNFa causes secretion of chemokines that stick to molecules on endothelial surface and cause neutrophil to stop rolling 6. Neutrophil is held on the endothelial surface by adhesion molecules and then squeezes through endothelium and moves up concentration gradient of cytokines to the site of infection
248
Describe the process of phagocytosis
1. Bacteria binds to the macrophage 2. Engluflment 3. Phagosome formation 4. Phagolysosome 5. Membrane disruption 6. Secretion of H2O2, NO and TNFa 7. MHC class II antigen presentation
249
What are the two pathways present in neutrophils and macrophages for microbial killing?
1. Oxygen dependent | 2. Oxygen independent
250
Describe 3 methods of O2 dependent method of microbial killing
1. Killing using reactive oxygen intermediates 2. Superoxides are converted to H2O2 then OH free radical 3. Nitric oxide which causes vasodilation increasing extravasation so more neutrophils in the tissue to kill pathogens
251
Describe the O2 independent method of microbial killing
Enzymes (Lysozyme) Proteins (Defensins inserted into membrane) pH
252
Name three characteristics that adaptive immunity has?
Antigen specificity and diversity Immunological memory Specific self and non-self recognition
253
What must the immune system do in order to be effective
Discriminate between self and non self
254
What is the function of lysozyme?
Destroys bacterial cell walls
255
In which primary lymphoid tissue do T cells mature?
Thymus
256
IN which primary lymphoid tissue do B cells mature?
Bone marrow
257
How do T cells recognise antigens?
For T cell recognition, antigens must be displayed by an antigen presenting cell bound to MHC1/2 - T cells cant recognise soluble antigens
258
What is the function of T-helper 1 (CD4)?
Helps the immune response against intracellular pathogens and secretes cytokines
259
What is the function of T-Helper 2 (CD4)
Helps to produce antibodies against extracellular pathogens and secretes cytokines
260
What is the function of cytotoxic T cell CD8
Kills cell directly by binding to antigens, inducing apoptosis
261
Which cells express MHC class I and why is it required
All nucleated cells ie a virus infected cell or cancer cell except erythrocytes CD8 Cytotoxic T cells required antigen to be associate with MHC I before they kill cell containing intracellular pathogen
262
Which cells express MHC class II and why is it required
Antigen presenting cells ONLY ie. macrophages, B cells and dendritic cells Helper T cells (CD4) requires MHC II before they help B cells to make antibodies to the extracellular pathogen
263
Which MHC would an intracellular antigen (Endogenous) lead to expression of?
MHC1
264
Which MHC would an extracellular antigen (Exogenous) lead to expression of?
MHC2
265
What type of T cell binds to MHC1
Cytotoxic T cells (CD8)
266
What type of T cells bind to MHC2
Helper T cells (CD4)
267
What does a helper T cell bind to?
A T cell receptor which is bound to an antigen epitope which bound to MHC2 on an APC
268
What happens to B cells that recognise 'self'?
They are killed in the bone marrow
269
Describe the process of a T helper cell binding to a B cell
1. A B cell binds an antigen 2. Phagocytosis 3. Epitope is displayed on the surface of the B-cell bound to an MHC2 4. TH2 binds the B cell 5. Cytokines secretion induces B cell clonal expansion 6. Differentiation into plasma cells and memory B cells
270
Which region of an antibody binds to antigens?
FAB region
271
Which region of an antibody binds to B cells
Fc region
272
Give examples of secondary lymphoid tissue
Spleen Lymph nodes Mucosa associated lymphoid tissue (MALT)
273
Where are complement system plasma protein derived from?
The liver
274
What activates the classical complement pathway?
Antibodies
275
What compound prevents excessive activation of the classical complement pathway
C1 inhibitor
276
What activates the lectin path of the complement pathway
mannose binding protein
277
What activates the alternate pathway of the complement pathway
Bacterial cell walls and endotoxin
278
What are PRR's a receptor for?
PAMPs
279
Name the three receptors that make up the PRR family
1. Toll like receptors 2. Nod-like receptors 3. Rig-like receptors
280
What is extravasation
Leukocyte migration across the endothelium
281
What do macrophages at the tissue secrete to initiate extravasation
TNFalpha
282
Define humoral immunity
Humoral immunity is immunity from serum antibodies produced by plasma cells that kills extracellular microbes
283
Define Cell mediated immunity
cell-mediated immunity can be acquired through T cells from someone who is immune to the target disease or infection. “Cell-mediated” refers to the fact that the response is carried out by cytotoxic cells - kills intracellular microbes
284
What are the two types of adaptive immunity?
Cell mediated | Humoral
285
What happens to T cells that recognise self?
They are killed in the foetal thymus
286
Intrinsic antigens are associated with which MHC class
Class I
287
Extrinsic antigens are associated with which MHC class
Class II
288
If the concentration of IL-12 is high, what does CD4 T cell become?
TH1
289
If the concentration of IL-12 is low, what does the CD4 T cell become?
TH2
290
Which of the following malignant tumours never metastasises? 1. malignant melanoma 2. Small cell carcinoma of the lung 3. Basal cell carcinoma of the skin 4. Breast cancer
Basal cell carcinoma of the skin
291
What is the name given to a malignant tumour of the striated muscle
Rhabdomyosarcoma
292
Which of the following tumours does not commonly metastasise to bone? 1. Bone cancer 2. Lung cancer 3. Prostate cancer 4. Liposarcoma
Liposarcoma
293
What term describes cancer that has not invaded through the basement membrane?
Carcinoma in situ
294
What is the name given to a benign tumour of glandular epithelium?
Adenoma
295
``` Which of the following cancers does not have a screening programme in the UK? 1. Breast 2. Colorectal 3. Cervical 4, Lung ```
Lung cancer
296
Which of the following is not a known carcinogen to humans? a. Hepatitis C (Will cause hepatocellular carcinoma) b. Ionising radiation c. Aromatic amines d. Aspergillus niger
Aspergillus Niger
297
What is the name of benign tumour of fat cells?
Lipoma
298
What is the name given to a malignant tumour of the glandular epithelium?
Adenocarcinoma
299
Which of the following is not a feature of malignant tumours? a. Vascular invasion b. Metastasis c. Increased cell divisions d. Growth related to overall body growth
Growth related to overall body growth
300
Can radon gas causes lung cancer?
YEs
301
Is a transitional carcinoma of the bladder a malignant tumour?
YEs
302
What is the name of a benign tumour of the smooth muscle
Leiomyoma
303
Which lifestyle factor is most likely to cause cancer? a. Drinking half. Bottle of wine a day b. Being obese c. Running for 20 mins twice a week d. Smoking 20 a day
Smoking 20 a day
304
Which tumour has the shortest median survival a. Basal cell carcinoma of the skin b. Malignant melanoma of the skin c. Breast cancer d. Anaplastic carcinoma of the thyroid
Anaplastic carcinoma of the thyroid
305
Does ovarian cancer commonly spread to the peritoneum?
Yes
306
Activation of naive T cells is best achieved by which antigen presenting cell? 1. Neutrophil 2. Mast cells 3. Macrophages 4. Dendritic cells
Dendritic cells
307
Which of the following cell types is located exclusively in tissues, has an important role in both the innate and adaptive immune system, are antigen presenting cells and have phagocytic properties 1. Macrophage 2. Neutrophil 3. Eosinophil 4. Mast cell 5. Fibroblast
Macrophage
308
Which of the following is not a barrier in the innate immune mechanism? 1. Anatomic barriers 2. Phagocytic 3. Inflammatory mechanisms 4. Antibody production 5. Skin
Antibody production
309
T cells recognise antigens 1. In solution in plasma 2. When presented on RBC's 3. Following presentation on antigen presenting cells 4. In a 3-dimensional form 5. Following presentation on pattern recognition receptors
Following presentation on antigen presenting cells
310
Influenza vaccine is targeted towards at risk groups in the Uk. Which of the following are classified as at risk? 1. Over 65 2. 16 years 3. Obese of any age 4. Teenagers 5. Under 2 years old
Over 65 | Under 2 years old
311
Which of the following is administered as a live attenuated vaccine in the uk? 1. Hep A 2. Measles, Mumps, Rubella 3. Tetanus 4. Flu 5. Polio
Measles, mumps and rubella
312
Complements are the proteins that are involved in the clearance of antigen/bacteria. Which of the following is not part of the elimination phase of complement activation 1. Opsonisation 2. Target cell lysis 3. Chemoattraction of leukocytes 4. Production of interferons 5. Phagocytosis
Production of interferons
313
Which of the following is a polyssacharide vaccine 1. Anthrax 2. Hib vaccine (Haemophilus influenza type b) 3. Rabies vaccine 4. Hepatitis A
Hib vaccine
314
Which of the following are features of the adaptive immune response? 1. Does not require prior contact with the pathogen 2. It works with B and T lymphocytes 3. Lacks Specificity 4. Distinguishes self from non-self 5. Enhanced by complement
It works with B and T lymphocytes
315
What are the two types of immune response in humans?
Innate and Acquired
316
Which of the following is not an organ specific auto-immune disease? 1. Ulcerative collitis 2. Type 1 diabetes mellitus 3. Graves disease 4. Hashimoto's Thyroiditis 5. Sjorgens syndrome
Ulcerative colitis
317
Which of the following is not a classical PAMP? 1. Peptidoglycan found in bacterial cell walls 2. Flagellin, a protein in bacterial flagella 3. Lipopolysaccharide from the outer membrane of gram negative bacteria 4. Interleukin 12 5. Nucleic acids such as viral DNA or RNA
Interleukin 12
318
How do antibodies protect against infection?
``` Neutralise toxins Immobilise motile microbes Prevent binding to and infection of host cells Form complexes Activate complement (IgG, IgM) Bind Fc receptors ```
319
Binding of Fc receptors to phagocytes causes what?
Enhanced phagocytosis
320
Binding of FC receptors to mast cells causes what?
Release of inflammatory mediators
321
Binding of FC receptors to NK cells causes what?
Enhanced killing of infected cells
322
What is the role of T helper cells (CD4+ve)
Help B cells make antibody Activate macrophages and NK cells help the development of cytotoxic T cells
323
What is the role of T cytotoxic cells (CD8+ve)
Recognise and kill infected host cells
324
What is the role of T regulatory cells
Suppress immune responses
325
What sort of antigens do B cells recognise?
Soluble, free and native antigens
326
What sort of antigens do T cells recognise?
Cell-associated processed antigen
327
Which gene codes for major histocompatibility proteins?
Major histocompatibility complex on chromosome 6 otherwise known as human leucocyte antigen (HLA)
328
What are the two subsets of Cd4 cells?
TH1 and Th2 cells
329
What Is the role of TH1 cells
1. Produce IL-2, y-interferon and TNFb 2. Activate macrophages leading inflammation 3. promote production of cytotoxic T cells 4. Induce B cells to make IgG antibodies
330
What is the role of TH2 cells
1. Produce IL-4,5,6,10 and 13 2. Activate eosinophils and mast cells Induce B cells to make iGE - promotes the release of inflammatory mediators ie. histamine from mast cells
331
How does the body handle bacteria and fungi?
Phagocytosis
332
How does the body handle viruses?
Cellular shut down Self-sacrifice Cellular resistance
333
What are the patterns that enable our immunity to determine between self and non-self?
1. Limited characteristics 2. Gram +ve bacteria have thick wall with no outer envelope 3. Gram -ve bacteria have thinner wall with outer envelope 4. DsRNa (Way of detecting viral infection 5. CpG motifs
334
What are the two types of pattern recognition receptors
Secreted and circulating | Cell associated
335
Name three receptors that's make up the PRR family
1. Toll like receptors 2. Nod like receptors 3. Rig like receptors
336
What is the main function of TLRs
TLRs send signals to the nucleus to secrete cytokines and interferons. These signals initiate tissue repair Enhanced TLR signalling I= improved immune response
337
What is the main function of NLRs
NLRs detect intracellular microbial pathogens | They release cytokines and can cause apoptosis if the cell is infected
338
What disease is caused by a non-functioning mutation in NOD2?
Crohns disease
339
What is the main function of RLR's?
RLR's detect intracellular double stranded RNA | This triggers interferon production and an antiviral response
340
TLRs are adapted to recognise damaged molecules. What characteristics do these damaged molecules often have in common
They are hydrophobic
341
What kind of TLRs can be used in vaccine adjutants?
TLR4 agonists
342
Give 3 examples of diseases that can be caused by PRRs failing to recognise pathogens
1. Atherosclerosis 2. COPD 3. Arthritis
343
Give examples of 3 extracellular PRR?
1. Mannose receptors 2. Scavenger receptors 3. TLRs
344
What is the function of mannose and scavenger extracellular receptors?
Induce pathogen engulfment
345
Give an example of an intracellular PRR
NLR
346
Where are circulating PRRs secreted from?
Epithelia, phagocytes and the liver where they can activate the complement cascade and induce phagocytosis
347
Give 2 examples of secreted and circulating PRRs
Antimicrobial peptides ie. Defensins and Cathelicidin Lectins and collectins ie. mannose binding lectin
348
What are cell associated PRRs and what is the main family?
Receptors that are present on the cell membrane on in the cytosol of cells TLRs
349
What is the ligand for TLR1/2
Gram positive lipopeptides
350
What is the exogenous ligand for TLR3
Double stranded RNA
351
What is the endogenous ligand for TLR3
mRNA
352
What is the exogenous ligand for TLR4
LPS Pneumolysin Viral Proteins
353
What are the endogenous ligands for TLR4
Heat shock proteins HMGB1 Hyaluronan Fibrinogen
354
What is the exogenous ligand for TLR5
Flagellin
355
What is the exogenous ligand for TLR2/6
Gram positive lipopeptides
356
What are the exogenous ligands for TLR7
Single stranded RNA
357
What are the exogenous ligands for TLR8
Single stranded RNA
358
What are the exogenous ligands for TLR9
CpG DNA
359
What are the three types of membrane bound PRR
Mannose receptor on macrophages Lectin 1 Scavenger receptors on macrophages
360
What do NLRs detect?
Peptidoglycan and muramyl dipeptide
361
What disease does a hyper functioning mutation in NOD2 lead to?
Blau Syndrome
362
What is the role of RLRs and give two examples
detect intracellular double stranded viral DNA and RNA | RIG-I and MDA5
363
Name three extracellular damage molecules
Fibrinogen Hyaluronic acid Tenascin C
364
Name 5 intracellular damage molecules
``` HMGB1 mRNA Heat shock proteins Uric acid and uric acid crystals Stathmin ```
365
Define passive immunisation
Give antibodies
366
Define active immunisation
Given dead/attenuated pathogens
367
What are the advantages of passive immunisation?
Immediate protection | Effective in immunocompromised patients
368
what are the advantages of active immunisation?
Dead- no risk of infection | Attenuated - immune response close to real thing
369
Disadvantages of passive immunisation
Short lived Serum sickness Does not activate immunological memory
370
What are the disadvantages of active immunisation?
Dead - just the humour response activated Attenuated - possible reversion to virulence Cant be given to an immunocompromised patient
371
Give some examples of passive immmunisation
Cross placement transfer of antibodies from mother to child (Natural) Treated with immunoserum or pooled human IgG (Artificial) - Human hepatitis B Ig - Varicella Zoster Ig
372
Give 2 examples of active immunisation
Non-living = Pertussis, infleunza, diphtheria and tetanus Attenuated = BCG, MMR, poliomyelitis
373
What are 5 patient risk factors when administering drugs?
1. polypharmacy 2. Old age 3. Genetics 4. Hepatic disease 5. Renal disease
374
What are 3 drug risk factors
1. Narrow therapeutic index 2. Steep dose/response curve 3. Saturable metabolism
375
What are the three types of adsorption?
Precipitation Chelation Neutralisation
376
What are the 4 types of drug interaction
1. Synergy 2. Antagonism 3. Summation 4. Potentiation
377
What is bioavailability
How much of the oral drug is in the system compared to how much of the IV drug
378
Does the ionised or unionised portion of a drug cross the bilayer?
Unionised
379
Where are most drugs metabolised?
Liver
380
Describe the metabolism of morphine?
Morphine metabolised by CYP450 pathway to morphine 6 glucuronide which enables excretion by the kidney
381
What is the effect of phenytoin on morphine metabolism
Phenytoin induces CYP450 enzymes leading to increased metabolism of morphine to active morphone 6 glucuronide = ENZYME INDUCTION
382
What is the effect of metronidazole on morphine metabolism?
Metronidazole slows CYP450 and reduces production of morphine 6 glucuronide so its less potent = ENZYME INHIBITION
383
Are weak basic drugs cleared faster if the urine is acidic or alkaline?
Acidic
384
Are weak acids drugs cleared faster if the urine is acidic or alkaline?
Alkaline
385
What drugs can induce acute kidney injury?
NSAIDs Gentamicin Furosemide ACEi
386
What is the affect of grapefruit juice in patients taking warfarin?
Affects CYP450 and warfarin ability to bind to proteins
387
Define a drug
A medicine or other substance which has a physiological effect when ingested or otherwise introduced into the body
388
Define pharmacology
Branch of medicine concerned with the use, effects and modes of action of drugs
389
Define pharmacodynamics
How the drug affects the body
390
Define pharmacokinetics
How the disposition of a compound within an organism - how the body affects a drug (ADME)
391
What is the main target for drugs
Proteins
392
Name 4 types of drug targets
receptors enzymes transporters Ion channels
393
Define receptor
Cell component that interacts with a specific ligand that initiates a change of biochemical events leading to observed effects
394
Give an example of a ligand gated ion channel
Nicotinic ACh receptor
395
Give an example of a GPCR
Muscarinic and β2 adrenoceptor.
396
Give an example of kinase-linked receptors
Receptors for growth factors
397
Give an example of cytosolic/nuclear receptors
Steroid receptors - modify gene transcription
398
Describe how GPCRs work
Activity regulated by factors that control the ability to bind and hydrolyse GTP to GDP
399
Give 2 examples of GPCRs
Muscarinic 3-receptor (Gq) | B2-AR (Gs)
400
What are kinase linked receptors?
Transmem receptor that are activated when the binding of extracellular ligand causes enzymatic activity on the intracellular side (Leads to protein phosphorylation)
401
Define agonist
A compound that binds to a receptor and activates it
402
Define antagonist
Antagonist decreases the effect of an agonist - shows no response at the receptor
403
Define potency
Measure of how well a drug works - EC50 = Concentration that gives half the maximal response
404
Define efficacy (Emax)
Maximum response achievable for a dose (Partial agonist will never achieve a full response)
405
Define intrinsic activity (Efficacy)
Ability of a drug receptor complex to produce a maximum functional response (Emax of partial agonist/ Emax of full agonist)
406
Would an antagonist shift the dose response curve to the left or to the right?
Shift to the right so a higher concentration of the agonist is required to achieve a full response - agonist becomes less potent
407
Define affinity
How well a ligand binds to a receptor
408
Define non-competitive antagonism
When the antagonist binds to an allosteric site on the receptor that disrupts its activation
409
What is the H1 histamine receptor associated with?
Allergic conditions
410
What is the H2 histamine receptor associated with?
Gastric acid secretion
411
What is the H3 histamine receptor associated with?
CNS disorders
412
What is the H4 histamine receptor associated with
Immune system and inflammatory conditions
413
What is the effect of fewer receptors on receptor response
Receptor response is still 100% due to receptor reserve (Partial agonists don't have a receptor reserve)
414
What is the affect of less signal amplification on drug response
Less signal amplification gives a reduced drug response
415
Define inverse agonism
When a drug binds to the same receptor as an agonist but induces a pharmacological response that is opposite to that of the agonist
416
Does an antagonist demonstrate efficacy
No, antagonist can have affinity but show zero efficacy. Agonist shows affinity and efficacy
417
Define tolerance
A reduction in the effect of a drug overtime due to continuous use of repeatedly high concentrations
418
Name 3 ways in which a receptor can be desensitised
1. Uncoupled 2. Internalised 3. Degraded
419
Define an enzyme inhibitor
a molecule that binds to an enzyme and decreases its normal activity
420
What are the two types of enzyme inhibitor
1. Irreversible - react with enzyme and change it chemically (Via covalent bond formation) 2. Reversible - Bind non-covalently
421
What do statins do?
Class of lipid lowering drugs that reduce the level of bad cholesterol by blocking' the rate limiting step in the cholesterol pathway
422
What is the effect of inhibiting ACE on blood pressue
inhibiting ACE prevents the conversion of Ang 1 to Ang 2 therefore causing a reduction in blood pressure
423
Name 2 ACE inhibitors
Captopril | Enalapril
424
What is the precursor molecule for L-DOPA
L-tyrosine
425
Which enzyme converts L-DOPA to dopamine>
DOPA decarboxylase
426
How does carbidopa works
Blocks DOPA decarboxylase in the periphery in the periphery which generates more L-DOPA for the CNS pathway
427
How do peripheral Catechol-O-methyl transferases (COMT) work? (Tolecapone) (Entacapone)
Peripheral COMT prevent L-DOPA breakdown therefore generating more for CNS pathway
428
How to central COMT inhibitors work? (Tolecapone)
Prevent the breakdown of dopamine in the central CNS
429
How do mono amine oxidase inhibitors such as selegiline and rasagiline work?
Prevent the breakdown of dopamine into DOPAC in the central CNS
430
How do uniporters work?
Use energy from ATP to pull molecules in
431
How do symporters work?
Use the movement in of one molecule to pull in another molecule against its concentration gradient
432
How do anti porters work?
One substance moves against its gradient using energy from a second substance that is moving down its gradient
433
Give an example of a symporter
NKCC2
434
How does furosemide work and what its it used for?
Used for oedema and hypertension Acts by inhibiting luminal NKCC2 in thick ascending limb Causes sodium, chloride and potassium loss in the urine
435
How does amiloride work?
Blocks epithelial sodium channels in the collecting ducts thus preventing sodium reabsorption - used as an antihypertensive
436
Where are voltage gated calcium channels found?
in membranes of excitable cells including muscle, glial cells and neurons
437
What does amlodipine do?
Calcium channel blocker that inhibits the movement of calcium into the vascular smooth muscle cells and cardiac muscle that inhibits contraction. This causes vasodilation, reduces peripheral vascular resistance and lowers blood pressure
438
What are the three conformational states a voltage gated sodium channel can be in
Closed Open Inactivated
439
How does lidocaine work?
Blocks the transmission of action potential and blocks signalling in the heart, reducing arrhythmia
440
Receptor mediated chloride channels respond to what ligands
Neurotransmitters such as GABA which opens the Cl- channel and causes membrane hyper polarisation
441
What compounds increase the permeability of chloride channels
Barbituates
442
How does the Na+/K+ ATPase work
Pumps 3Na+ out the cell for every 2K+ it returns to the cell
443
How does digoxin work?
Inhibits Na+/K+ in the myocardium which increase intracellular Na+ resulting in decreased activity of the Na+/Ca2+ exchanger which increases intracellular Ca2+, lengthening the cardiac action potential leading to a decrease in heart rate
444
What is the role of the K+/H+ ATPase?
Responsible for the acidification of the stomach and the activation of the digestive enzyme pepsin
445
How does omeprazole work?
Inhibits irreversibly H+/K+ ATPase
446
Organophosphates such as insecticides and nerve gas are irreversible inhibitors of what?
Cholinesterases
447
Aspirin is an irreversible inhibitor of what?
COX
448
What is a xenobiotic?
A compound foreign to an organisms normal biochemistry such as a drug or a poison
449
What are the two divisions of the autonomic nervous system
Sympathetic and parasympathetic
450
What are the 6 regulatory roles of the autonomic nervous system?
1. Vascular 2. Airway 3. Visceral smooth muscle 4. Exocrine secretions 5. Control of heart rate 6. Energy metabolism in the liver
451
Where are parasympathetic ganglia located?
Near their targets with short post ganglionic fibres and long pre-ganglionic fibres
452
Where are sympathetic ganglia located?
Near the spinal cord with short pre-ganglionic fibres and longer post-ganglionic fibres
453
Which cranial nerves are parasympathetic
Oculomotor (CNIII) Facial (VII) IX X
454
Which hormone Is released on the pre-ganglionic parasympathetic fibres to act on nicotinic receptors
ACh
455
Which hormone is release on the post-ganglionic parasympathetic fibres to act on muscarinic receptors
ACh
456
Which hormone is released on the pre-ganglionic sympathetic fibres to act on nicotinic receptors
ACh
457
Which hormone is released on post-ganglionic sympathetic fibres to act on alpha and beta adrenergic receptors?
Noradrenaline
458
Which parts of the body are under sympathetic control only?
Sweat glands | Blood vessels
459
Which part of the body is under parasympathetic control only?
Bronchial smooth muscle
460
Which parts of the body are under dual sympathetic and parasympathetic control
Gut, bladder, heart
461
Name 4 non-adrenergic and non cholinergic autonomic transmitters used by the enteric, sympa and parasympathetic NS
Nitric oxide Vasoactive intestinal peptide ATP Neuropeptide Y
462
Which enzymes is responsible for the breakdown of acetylcholine in the synaptic cleft
Acetylcholinesterase
463
What type of receptor is muscarinic receptors and how many classes are there?
GPCR | M1-M4
464
Where are M1 muscarinic found in the body?
Brain
465
Where are M2 muscarinic receptors found in the body and what does their activation cause
Found in the heart, activation slows the heart (Bradycardias) - can be blocked with atropine
466
Where are M3 muscarinic receptors found in the body and what does their activation cause
Found in the glandular and smooth muscle | - cause bronchoconstriction, sweating and saliva secretion
467
Where are M4 muscarinic receptors found in the body
In the CNS
468
What does pilocarpine do and when might it be useful
Stimulates salivation - may be useful after radiotherapy of head and neck or sjorgens syndrome
469
Name a muscarinic antagonist and what condition may it be used to treat
Atropine | Used to prevent bradycardia, prevent BP drop and dry up secretions perioperatively
470
Name two different types of anti-muscarinics used in the treatment of bronchoconstriction
Short acting - Ipratropium bromide | Long acting - LAMAs including tiotropium and glycopyrrhonium
471
What is solifenacin and what is it used for?
Anticholinergic | Used to treat overactive bladder
472
What are suxamethonium and pancuronium and what are they used for?
Inhibit muscle activity and induce relaxation in surgery by inhibiting nicotinic blockers
473
What are the side effects of anti-cholinergics?
``` COnstipation Dry mouth blurring of vision Worsening of glaucoma Worsen memory and cause confusion ```
474
What is the precursor molecule for adrenaline and noradrenaline
Dopamine
475
What is the primary agonist of alpha 1 receptors
Noradrenaline > Adrenaline
476
What is the mechanism of action act alpha 1 adrenergic receptors and what are the consequences
Activation increases intracellular calcium (Gq signalling) Leads to smooth muscle contraction (pupil, blood vessels) = vasoconstriction bladder contraction
477
What is the primary agonist of alpha 2 receptors
Noradrenaline and adrenaline activate equally
478
What is the mechanism of action at alpha 2 adrenergic receptors and what are the consequences
Gi signalling - Inhibition of cAMP generation | Mixed effects on smooth muscle
479
What is the primary agonist of beta 1 receptors
Noradrenaline and adrenaline are equal
480
What is the mechanism of action at beta 1 adrenergic receptors and what are the consequences
Gs - raises levels of cAMP Increases the chronotropic and inotropic effects on heart Increased renin release from kidney which increases blood pressure
481
What is the primary agonist of beta 2 adrenergic receptors
Adrenaline > Noradrenaline
482
What is the mechanism of action at beta 2 adrenergic receptors and wha are the consequences
``` Gs - Raises cAMP Relaxes smooth muscle in premature labour and asthma Bronchodilation vasodilation Reduced GI motility ```
483
What is the primary agonist at beta 3 adrenergic receptors
Noradrenaline > Adrenaline
484
What is the mechanism of action at beta 3 adrenergic receptors and what is the consequence
Gs - raises cAMP | Enhances lipolysis and relaxes the bladder detrusor muscle
485
When might an Alpha 1 agonist be used?
In the treatment of septic shock to cause vasoconstriction and prevent a drop in blood pressure
486
What is Doxazosin and when is it used?
Alpha 1 antagonist that blocks alpha 1 receptors to lower blood pressure
487
What is tamsulosin and when is it used
Alpha 1a antagonist used in the prostate to prevent prostatic hypertrophy
488
What does beta 1 adrenergic receptor activation do?
Increase HR and chronotropic effects | Increases the risk of arrhythmias
489
What does propranolol block and what are the consequences
``` Beta 1 (Heart) and beta 2 (lungs) Slows the HR, reduces tremor and may cause wheeze ```
490
What does atenolol block and what are the consequences
``` Beta 1 (heart) selective Lowers the blood pressure by reducing cardiac output and gradual reduction in sympathetic outflow ```
491
What are the uses of beta blockers?
``` Angina MI prevention High blood pressure Anxiety Arrhythmias Heart failures ```
492
What are the side effects of beta blockers
``` Tiredness Cold extremities Bronchoconstriction Bradycardia Hypoglycaemia Cardiac depression ```
493
Define hypersensitivity
Excessive response that can be mediated immediately, acutely or gradually
494
How many different types of hypersensitivity reaction are there according to Gell and Coombs
4
495
What is a type 1 hypersensitivity reaction and name some examples
Immunological memory to something causing an allergic reaction - IgE Anaphylaxis, Asthma and hay fever
496
What are the two potential routes of exposure in a type 1 hypersensitivity reaction
Local Exposure - Hayfever from pollens, animals, occupational exposure Systemic exposure - Drugs, foods, treatments
497
What are the effects of histamine release
Vasodilation and capillary leakage
498
What do mast cell granules contain
``` Histamine PGD2 Proteases Cytokines IL-4 IL-13 TNFa ```
499
Define atopy
Inherited tendency to an exaggerated IgE response to an antigen
500
What are 4 treatments for hay fever?
Prevent exposure Anti-histamines Reduction in local inflammation (Steroids) Desensitisation
501
What are the treatments for anaphylaxis
``` Avoid/cease exposure Stop acute symptoms (anti-histamines) Acute resuscitation (Adrenaline, fluids, bronchodilators) Decrease inflammation (Steroids) Intramuscular adrenaline to maintain circulation ```
502
Describe a phase 2 hypersensitivity reaction
Immunoglobulins (IgG) bound to surface antigens which causes the immune system to attack the basement membrane of the kidney and lungs
503
Give 4 examples type 2 hypersensitivity reaction
Goodpastures syndrome Mycoplasma Pneumonia Graves Disease Myaesenthia Gravis
504
Describe a type 3 hypersensitivity reaction
Antibodies and target circulate. Little lumps of antibody and target get deposited in the skin, lung and kidneys and activate immunity so phagocytes go and destroy it resulting in capillary damage in lungs and kidneys
505
Give an example of a type 3 hypersensitivity reaction
Extrinsic Allergic Alveolitis | Formation of precipitating antibodies to organic dusts
506
What are the 4 types of extrinsic allergic alveolitis
Farmers lung Malt workers lung Mushroom workers lung Pigeon Fanciers Lung
507
Describe type 4 hypersensitivity reactions
Formation of granulomas dependent on the activation of T cells
508
Give an example of a type 4 hypersensitivity reaction
TB | Sarcoidosis
509
Name two opioids that are naturally occurring
Codeine | Morphine
510
Name three opioids formed from simple chemical modifications
Diamorphine Oxycodone Dihydrocodeine
511
Name 4 synthetic opioids
Penthidine Fentanyl Alfentanil Remifentanil
512
Name a synthetic partial opioid agonist
Buprenorphine
513
Name an opioid antagonist
Naloxone
514
What is the most common route of administration of opioids and what is the normal dose via this method
Oral - 10mg half the dose for s/c, IM or IV
515
What is diamorphine otherwise known as?
Heroin
516
How do opioids work
Use the existing pain modulation system | Inhibit the release of pain transmitters at spinal cord and midbrain and modulate pain perception in higher centres
517
What are the receptors that opioids bind to?
Mu, delta, kappa
518
Define tolerance
Downregulation of receptors due to prolonged use - results in a need for higher dose to achieve the same effect
519
Define dependence
Psychological - craving, euphoria and physical
520
How long does opioid withdrawal last
72 hours
521
What are the side effects of opioid administration
1. respiratory depression 2. Sedation 3. Nausea and vomiting 4. Constipation 5. Itching 6. Immune system suppression 7. Endocrine effects
522
What is the treatment for opioid induced respiratory depression
1. Call for help 2. ABC 3. Naloxone - 400ug/ml - titrate to effect ie. dilute 1ml in 10ml saline 4. IV fastest route
523
Give an example of a prodrug
Codeine | Tramadol
524
Which enzyme is required to metabolise codeine to its active form
CYP2D6
525
What is morphine metabolised to by CYP2D6
Morphine 6 glucuronide
526
What enzyme is required to metabolic tramadol into its active form?
CYP2D6
527
What is tramadol metabolised to by CYP2D6?
O-desmethyl tramadol
528
Define an adverse drug reaction
Unwanted or harmful reaction following administration of a drug or combination of drugs under normal conditions of use and is suspected to be drug related - needs to be noxious and unintended
529
Define side effects
Unintended effect of a drug relate to its pharmacological properties and can include expected benefits of treatment
530
What are the 3 types of adverse drug reaction
1. Toxic effects - drug applied beyond therapeutic range 2. Collateral effects - Use drug within its therapeutic range 3. Hypersusceptibility effects - drug used below its therapeutic range
531
What are the causes of a toxic ADR?
Administration of a too high dose Drug excretion reduced by renal or hepatic functional impairment Interactions with other drugs
532
What are 4 symptoms of a mild adverse drug reaction?
Nausea Drowsiness Itching Rash
533
What are 4 symptoms of a severe adverse drug reaction?
Respiratory depression Neutropenia Catastrophic haemorrhage Anaphylaxis
534
Define a time independent adverse drug reaction
One that can occur at any time during treatment
535
What are the 6 types of time dependent adverse drug reaction?
1. Rapid reaction 2. First dose reaction 3. Early reaction 4. Intermediate Reaction 5. Late reaction 6. Delayed reaction
536
What is the Rawlins Thompson adverse drug reaction classification
1. Type A = Augmented pharmacological (Predictable and dose dependent - extension of the primary effect) 2. Type B = Bizarre or idiosyncratic (Not predictable or dose dependent) 3. Type C = Chronic 4. Type D = delayed 5. Type E = End of treatment 6. Type F = Failure of therapy
537
What is the DoTS classification of an adverse drug reaction?
Dose relatedness (Toxic, collateral or hypersusceptibility) Timing Patient susceptibility
538
What are the patient risk factors for an adverse drug reaction?
``` Gender (F>M) Elderly Neonates Polypharmacy Genetic disposition Hypersensitivity/allergies Hepatic/renal impairment Adherence problems ```
539
What are the drug risk factors for an adverse drug reaction?
Steep dose response curve Low therapeutic index Commonly causes ADRs
540
What are the prescriber risk factors for an adverse drug reaction?
Prescriber may be busy or tired leading them to not realise that two drugs interacting may cause an ADR
541
What are the 7 causes of an ADR?
1. Pharmacological variation 2. Receptor abnormality 3. Abnormal biological system unmasked by the drug 4. Abnormalities in drug metabolism 5. Immunological 6. Drug-drug interactions 7. Multifactorial
542
Give an example of a type A augmented ADR
Administration of insulin causing hypoglycaemia Administration of propranolol causing bradycardia
543
Give an example of a type C continuous ADR
Prolonged use of steroids causes thinning of the bones leading to osteoporosis
544
Give an example of a type D delayed ADR
teratogenesis - drugs taken in the first trimester ie. thalidomide
545
Give an example of a type E end of treatment ADR
Get withdrawal seizures when anti-convulsants are stopped
546
When should we suspect an ADR?
1. Symptoms soon after a drug is started 2. Symptoms after a dosage increase 3. Symptoms disappear when the drug is stopped 4. Symptoms when the drug is restarted
547
What are the most commonly administered drugs that cause ADRs
``` Antibiotics Anti-neoplastics Cardiovascular drugs Hypoglycaemics NSAIDs CNS drugs ```
548
What are the most common systems to be affected by ADRs
``` GI Renal Haemorrhagic Metabolic Endocrine Dermatologic ```
549
What is the role of the medicines and healthcare products regulatory agency
Responsible for ensuring medicines and medical devices work and are acceptably safe
550
What are the strengths of the yellow card scheme
- Early warning for previously unrecognised reactions - Provides information about factors which predispose patients to ADRs - Allows ADR comparison between products of same therapeutic class - Continual safe monitoring of product throughout life span
551
What are the weaknesses of the yellow card scheme
- Cannot provide estimate of risk as true number of cases is underestimated and total number of exposed patients is unknown - Relies on ADR being recognised - Not all ADRs reported - May be stimulated by promotion or publicity - Reporting high for newly marketed drugs and then falls off over time
552
Why are yellow card reporting rates low
``` Ignorance Diffidence Fear Lethargy Guilt Ambition Complacency ```
553
Why should we report ADRs?
``` Patient safety Identify ADRs not indentified in clinical trials Identify new ADRs ASAP Compare drugs in same therapeutic class Identify ADRs in at risk groups ```
554
What should be reported on a yellow card?
Suspected reactions for herbal medicines and black triangle drugs All serious suspected reactions for drugs, vaccines, contrast media
555
What defines a serious adverse drug reaction
``` is fatal is life threatening Is disabling results in hospitalisation prolongs hospitalisation ```
556
Define hypersensitivity
Objectively reproducible symptoms or signs initiated by exposure to a defined stimulus at a dose tolerated by normal subjects and may be caused by immunologic (allergic) or non immunologic mechanisms
557
Describe what happens in a type 1 hypersensitivity reaction
1. Prior exposure to antigen/drug 2. IgE antibodies formed after exposure 3. IgE becomes attached to mast cell and expressed as cell surface receptor 4. Re-exposure causes mast cell degranulation and release of pharmacologically active substances such as histamine
558
Give an example of a type 1 hypersensitivity reaction
Anaphylaxis
559
What occurs during an anaphylactic reaction
``` Vasodilation which causes increased vascular permeability leading to swelling and oedema Bronchoconstriction urticaria Angio-oedema hypotension Wheeze ```
560
Describe what happens in a type 2 hypersensitivity reaction
Antibody dependent cytotoxicity - - Drug combines with protein - Body treats it as foreign proteins and forms antibodies - Antibodies combine with antigen and complement activation damages the cells
561
Describe what happens during a type 3 hypersensitivity reaction
Immune complex mediated - Antigen and IgG antibody form large complexes and activate complement - small blood vessels are damaged or blocked - Leucocytes are attracted to site and release proinflammtory molecules
562
Give an example of a type 3 hypersensitivity reaction
Glomerularnephritis
563
Describe what happens in a type 4 hypersensitivity reaction
Antigen specific receptors develop on T-lymphocytes and subsequent administration leads to local tissue allergic reaction
564
Give an example of a type 4 hypersensitivity reaction
Contact dermatitis | TB
565
Describe a non-immune anaphylaxis
Direct degranulation of mast cells caused directly by the drug with no previous exposure - Clinically identical to immune anaphylaxis
566
Describe the management of anaphylaxis
``` Begin life support (ABC) Stop the exposure ie. IV fluid Give Adrenaline (500um) High Flow oxygen IV fluids to maintain blood pressure Anti-histamines (Chlorphenamine) Steroids (Hydrocortisone) ```
567
What are the effects of adrenaline administration to an individual having anaphylaxis
1. Vasoconstriction - increase peripheral vascular resistance to increase bp via A1 adrenoceptors 2. Stimulate B1 adrenoceptors to increase chronotropic and inotropic effects on heart 3. Reduce oedema and bronco dilate via beta2 adrenoceptors 4. Attenuate further release of mediators from mast cells and basophils by increasing intracellular c-AMP which reduces inflammatory mediators
568
What are the risk factors for hypersensitivity
``` Protein or polysaccharides based drugs Female > males HIV patients Previous drug reactions Uncontrollled asthma Certain HLA groups Acetylator status ```
569
What is the clinical criteria for an allergy to a drug
1. Does not correlate with pharmacological properties of drug 2. No linear relation with dose 3. Reaction similar to those produced by other allergens 4. Induction period of primary exposure 5. Disappearance on cessation 6. Re-appears on re-exposure 7. Occurs in minority of patients on drug
570
What are the two different apoptosis pathways?
``` intrinsic = Bcl-2 and Bax Extrinsic = Fas ligand ```
571
Give some examples of disease causes by inherited genetic abnormalities
CF Sickle cell huntingtons
572
Give some examples of diseases caused by spontaneous mutations
``` Downs = trisomy 21 Edwards = trisomy 18 Pataus = trisomy 13 ```
573
Give an example of an environmental disease
Foetal alcohol syndrome
574
Give some examples of mutlifactorial disease
Spina bifida Anencephaly Hydrocephaly
575
Define atrophy
Decrease in the size of cell tissue due to reduction in cell size and number often due to apoptosis
576
How are malignant tumours classified?
Grade 1 = well differentiated Grade 2 = moderately differentiated Grade 3 = Poorly differentiated (Most aggressive)
577
What is a teratoma
Neoplasm of germ cell origin that forms cells affecting all three germ cell layers
578
Which cancers are screened for in the UK
Cervical Breast Colorectal
579
What is the function of the immune system?
Discriminate between self and non-self
580
What is the role of the complement system
Remove or destroy antigens either by direct lysis or opsonisation
581
Describe the process of complement activation
2 phase 1. Activation of C3 2. Activation of the lytic pathway
582
Which enzyme is responsible for cleaving C3 to activate the complement system
C3 convertase
583
When C3 is cleaved, what are the products
C3b = mediates opsonisation and lysis C3a = Enhances inflammation by stimulating mast cells to secrete histamines
584
What are the three pathways that C3 can be cleaved
Classical Alternative Lectin
585
What is an antibody
A protein produced in response to an antigen that can only bind with the antigen that induced its formation
586
What is an epitope
Part of an antigen that binds to the antibody binding site
587
Describe the basic structure of an antibody
Four chains, two light and two heavy Constant and variable region FAB region binds to antigens FC region binds complement and Fc receptors on phagocytes and NK cells
588
What are the functions of antibodies
1. Neutralise toxins (IgG and A) 2. Immobilise microbe (IgM) 3. Increase opsonisation 4. Activate complement (IgG and IgM 5. Bind Fc receptors on phagocytes, mast cells and NK cells
589
What are PAMPs, why are they important and give one example
Pathogen associated molecular patterns Allows the innate immune system to recognise pathogens LPS
590
What are the PRRs and what are the two different types
Pattern recognition receptors 1. Secreted and circulating 2. Cell associated
591
Name the three different types of secreted and circulating PRRs
Antimicrobials = defensins and cathelicidins Lectin and collectins Pentraxin
592
Name the cell associated PRRs
Toll like receptors Nod like receptors Rig like receptors
593
NLR detect what?
Muramyl dipeptide and peptidoglycan
594
RLR detect what?
Intracellular double stranded RNA and DNA
595
Why do we need an adaptive immunity?
Microbes evade the innate Intracellular viruses and bacteria hide Need memory to specific antigen
596
What is the function of MHC
Present antigenic material to T cells
597
Define Atopy
Inherited tendancy to overproduce IgE in response to common environmental antigens
598
What is natural passive immunity
Transfer of maternal antibodies across the placenta to foetus
599
Natural passive immunity provides protection from what diseases
``` Diptheria Tetanus Streptococcus Rubella Mumps Polio ```
600
What are the two types of whole organism vaccine
Live attenuated | Killed inactivated
601
What diseases does a live attenuated vaccine protect against
Tuberculosis Pollo sabin Typhoid Mumps
602
What diseases does a killed inactivated vaccine protect against
Anthrax Cholera Hep A
603
What is an adjuvant
Any substance added to a vaccine to stimulate the immune system
604
What are the two divisions of the peripheral nervous system
Autonomic | Somatic
605
What are the adverse effects of muscarinic agonists (DUMBELS)
``` Diarrhoea Urination Miosis (Excessive pupil constriction) Bradycardia Emesis Lacrimation Salivation/sweating ```
606
What GPCR is A1 adrenoceptor
Gq + PLC
607
What GPCR is A2 adrenoceptor
Gi
608
What GPCR are Beta adrenoceptors
Gs
609
Name an alpha 2 adrenoceptor antagonist
Yohimbine
610
Define pain
Unpleasant sensory + emotional experience associated with actual and potential tissue damage
611
Define absorption
Process of transfer from the site of administration into the general or systemic circulation
612
What are the routes of drug administration
``` Oral IV Intra-arterial IM SC Inhalation Topical Sublingual Rectal Intrathecal (Into spinal canal) ```
613
How do drugs get across membranes
1. Passive diffusion through lipid layer 2. Diffusion through pores or ion channels 3. Carrier mediated processes 4. Pinocytosis
614
Rate of diffusion is proportional to what?
Area of the membrane | Permeability of the membrane
615
Rate of diffusion is inversely proportional to what?
Membrane thickness
616
Carrier mediated transport requires what?
ATP - moves molecules against a concentration gradient
617
Facilitated diffusion occurs using which gradients
Concentration gradient | Electrochemical gradient
618
Define pinocytosis
Form of carrier mediated entry into the cytoplasm
619
Name a drug that is transported by pinocytosis
Amphotericin
620
What forms are a drug normaly in
Weak acid | Weak base
621
What does the extent of ionisation depend on
Strength of the ionisable group | pH of the solution
622
Is the ionised form water or lipid soluble
Water soluble
623
Is unionised form water or lipid soluble
Lipid soluble
624
What is the pKa of a drug
pH at which half of the substance is ionised and half is unionised
625
Where are weak acids best absorbed
In the stomach
626
Where are weak bases best absorbed
in the intestine
627
Why is the oral route most commonly preferred
because large surface area with a high blood flow
628
For a drug to cross the phospholipid bilayer it needs to be what?
Lipid soluble
629
What factors slow gastric emptying and hence drug absorption?
Food Drugs Trauma
630
What factors increase gastric emptying and hence drug absorption
Gastric surgery (Gastrectomy) (Plyloroplasty)
631
Why can some drugs not be given orally
Because they are unstable at low pH or in the presence of digestive enzymes
632
What 4 barriers do drugs taken orally have to pass to reach the circulation
1. Intestinal lumen 2. Intestinal wall 3. Liver 4. Lungs
633
What is broken down by enzymes of the intestinal lumen
Peptide drugs broken down by proteases
634
luminal membrane of enterocytes contain what which can limit the absorption of a drug
P-glycoproteins
635
1st pass metabolism occurs mainly where?
in liver
636
How can you avoid first pass metabolism
Give drug to region of the gut not drained by splanchnic ie. mouth or the rectum
637
Name a drug given transcutaneously
Fentanyl patch in chronic pain (Non potent- non irritant drugs Delivered slowly
638
Name a drug given intradermally or subcutaneously
Local anaesthetic Insulin (Sc) Can deliberately limit the rate of absorption
639
What is the issue with IM injections
Dependent of blood Flow and water solubility - increase in either will enhance the removal of the drug from the injection site
640
Name a benefit of intranasal administration
Large surface area
641
Name an advantage and one disadvantage of inhalation administration
Large surface area but limited by risk of toxicity to the alveoli
642
Define distribution
Process by which the drug is transferred from the general circulation to the tissues as the blood concentration increases and then returns from the tissues to the blood when the concentration falls
643
Describe how IV drugs become distribute
Initial high plasma concentration and drug rapidly enters well perfused tissues but drug will continue to enter less well perfused tissues lowering plasma concentration so concentration in highly perfused tissues then begins to decrease
644
what are the components of the blood brain barrier
Tight junctions Small numbers and sizes of pores in the endothelium Astrocytes
645
What is the role of efflux transporters in the BBB
Protect the brain by returning drug molecules to the circulation
646
How are drugs removed from the BBB
Diffusion into the plasma Active transport in the choroid plexus Elimination in CSF
647
Do lipid soluble drugs cross the placenta
Yes
648
Define elimination
Removal of a drugs activity from the body
649
Define metabolism
Transformation of a drug molecule into a different molecule
650
Define excretion
Molecule expelled in liquid, solid or gaseous waste
651
Describe a phase I reaction
Reaction that involves the transformation of a drug to a more polar metabolite Addition of functional group
652
What is the most common phase I reaction
Oxidation - catalysed by cytochrome P450
653
Where are the CYP450 enzymes located
In the smooth endoplasmic reticulum in the liver
654
What can induce P450 enzymes
Smoking Alcohol Drugs Food
655
What is a phase 2 reaction
Conjugation - formation of a covalent bond between the drug or its phase 1 metabolite and an endogenous substrate - resulting products are usually less active and readily excreted by the kidneys
656
What are phase 1 metabolites usually conjugated with?
Glucuronic acid | Acetyl methyl groups
657
How are molecular weight polar compounds excreted
``` In fluids Urine Bile sweat tears Breast milk ```
658
High molecular weight compounds are excreted by
Solid | Faecal
659
Volatile drugs are excreted by
Gas
660
Write an equation for total excretion
Glomerular filtration + tubular secretion - reabsortption
661
Describe enterohepatic circulation
HMW molecules taken into hepatocytes and eliminated in the bile Bile passes down the gut and some drug may be reabsorbed and enters hepatic portal vein via enterohepatic circulation
Phase 2
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