Introduction to clinical sciences Flashcards
1
Q
What are the 2 types of autopsy
A
Hospital Autopsy
Medico-legal Autopsy
2
Q
What are hospital autopsies useful for, and what % of UK autopsies are they
A
Useful for audit, teaching, governance, research
10% of all UK autopsies
3
Q
What are Medico-legal autopsies useful for, and what % of UK autopsies are they
A
Coronial autopsies – standard
Forensic autopsies – deaths involving crime
90% of all autopsies in the UK
4
Q
What is presumed natural death (coroners)
A
Cause of death not known
Not seen by doctor with recent illness (last 14 days)
5
Q
what is presumed iatrogenic death (coroners)
A
Peri/postoperative deaths
Anaesthetic deaths
Abortion
Complications of therapy
6
Q
What are presumed unnatural deaths (coroners)
A
Accidents
Industrial death
Suicide
Unlawful killing (murder)
Neglect
Custody deaths
7
Q
What is Inflammation
A
the local physiological response to tissue injury.
8
Q
What are beneficial effects of Inflammation
A
Destruction of invading microorganisms
The walling off of an abscess cavity, thus preventing spread of infection
9
Q
What are problems caused by inflammation
A
An abscess in the brain would act as a space-occupying lesion compressing vital surrounding structures
Fibrosis resulting from chronic inflammation may distort the tissues and permanently alter their function
10
Q
What are the cells involved in inflammation
A
Neutrophils
Macrophages
Lymphocytes
Endothelial cells
Fibroblasts
11
Q
Role of Neutrophils in inflammation
A
Short lived cells
First on the scene of acute inflammation
Cytoplasmic granules full of enzymes that kill bacteria
Usually die at the scene of inflammation
Release chemicals that attract other inflammatory cells such as macrophages
12
Q
Role of Macrophages in inflammation
A
Long lived cells (weeks to months)
Phagocytic properties
Ingest bacteria and debris
May carry debris away
May present antigen to lymphocytes
13
Q
What are the names of macrophages based on location (liver, skin, bone, brain.)
A
Kupffer cell (liver), melanophage (skin), osteoclast (bone), microglial cell (brain)
14
Q
Role of Lymphocytes in inflammation
A
Long lived cells (years)
Produce chemicals which attract in other inflammatory cells
Immunological memory for past infections and antigens
15
Q
Role of Endothelial cells in inflammation
A
Line capillary blood vessels in areas of inflammation
Become sticky in areas of inflammation so inflammatory cells adhere to them
Become porous to allow inflammatory cells to pass into tissues
Grow into areas of damage to form new capillary vessels
16
Q
Role of Fibroblasts in inflammation
A
Long lived cells
Form collagen in areas of chronic inflammation and repair
17
Q
What is Acute Inflammation
A
the initial and often transient series of tissue reactions to injury
Sudden onset
Short duration
Usually resolves
18
Q
What are the 3 processes of Acute inflammation
A
Vascular component: dilatation of vessels
Exudative component: vascular leakage of protein – rich fluid
Neutrophils recruited to the tissue
19
Q
What are the potential outcomes of Acute Inflammation
A
Resolution
Suppuration
Organisation
Progression to chronic inflammation
20
Q
What is Resolution (acute inflammation)
A
the complete restoration of the tissues to normal after an episode of acute inflammation.
21
Q
What is Supperation (acute inflammation)
A
(e.g. abscess) – the formation of pus, a mixture of living, dying and dead neutrophils and bacteria, cellular debris and globules of lipid.
22
Q
What is Organisation (Acute inflammation)
A
the process whereby specialised tissues are repaired by the formation of mature fibrovascular connective tissue. It occurs by the production of granulation tissue and the removal of dead tissue by phagocytosis.
23
Q
What are 6 causes of Acute Inflammation
A
Microbial infections e.g. viruses
Hypersensitivity reactions e.g. parasites
Physical agents e.g. trauma/ radiation
Chemicals e.g. corrosives/ acids
Bacterial toxins
Tissue necrosis e.g. ischaemic infarction
24
Q
What is Chronic inflammation
A
the subsequent and often prolonged tissue reactions following the initial inflammatory response
Slow onset
Long duration
May never resolve
25
What are the causes of chronic inflammation
Primary chronic inflammation
Transplant rejection
Progression from acute inflammation
Recurrent episodes of acute inflammation
26
What are the main cells involved in chronic inflammation
macrophages, Lymphocytes, plasma cells
27
What are the main cells involved in Acute inflammation
Neutrophils
28
What are Granulomas
a collection of epithelioid histiocytes (macrophages).
29
What is Granulation tissue
repair phenomenon, it is loops of capillaries supported by myofibroblasts which actively contracts to reduce wound size, this may leave a structure present
30
What does Ibuprofen do?
inhibit prostaglandins synthetase, decrease inflammation
31
What are Prostaglandins
chemical mediators of inflammation
32
describe the process and recovery for Lobar pneumonia
Affects a lobe of the lung rather than the whole thing (bronchopneumonia)
Alveoli filled with neutrophil polymorphs (acute inflammation) rather than air
Pneumocyte that line the alveoli can regenerate so the lung can be regenerated – the pneumocytes divide and reline the alveoli
33
Describe what skin abrasions are and their process of healing
The most superficial skin wounds e.g. road rash
Normal skin -> abrasion -> scab formed over surface -> epidermis growing out from adnexa, produced by scab -> thin confluent epidermis -> final epidermal regrowth
34
What is healing by 1st intention for incised skin wounds
An incision causes very little damage to the tissues on either side of the cut, so if the two sides are brought together accurately the healing can proceed quite quickly.
1st intention – can suture up the cut
Incision -> exudation of fibrinogen -> weak fibrin join -> epidermal regrowth and collagen synthesis -> strong collagen join
35
What is healing by 2nd intention for tissue loss injuries
A tissue loss injury or another reason that the wound margins are not apposed requires another mechanism for repair.
Can’t bring the skin edges together the cut is too deep
Loss of tissue -> granulation tissue -> organisation -> early fibrous scar -> scar contraction
Phagocytosis to remove any debris
Granulation tissue to fill in defects and repair specialised tissues lost
Epithelial regeneration to cover the surface
36
What is repair (vs healing)
Initiating factor still present
Tissue damaged and unable to regenerate
Replacement of damaged tissue by fibrous tissue
Collagen produced by fibroblasts
37
What cells don't regenerate
Myocardial cells
Neurones
38
What cells regenerate
Hepatocytes
Pneumocytes
All blood cells
Gut epithelium
Skin epithelium
Osteocytes – help remodel bone fractures
39
Why are blood clots rare in normal physiology
Laminar flow – cells travel in the centre of arterial vessels and don’t touch the sides
Endothelial cells which line vessels are not ‘sticky’ when healthy
40
Define Thrombus
solid mass of blood constituents formed within intact vascular system during life
41
What are the steps of thrombus formation
1. Damage to endothelial cells in the vessel causes some of the cells to lift away from the vessel wall, exposing collagen.
2. Platelets then begin to stick to this exposed collagen, and release the chemicals which cause platelet aggregation. Platelet aggregation also starts off the cascade of clotting proteins in the blood.
3. Red blood cells then get trapped within the aggregating platelets
4. Clotting factors join the red blood cells and platelets, and the clotting cascade forms a large protein molecule fibrin, which then gets deposited and forms the clot.
5. Positive feedback loop -> can end up causing a thrombus (thrombosis), blocking the artery
42
What is the Virchow triad
the causes of thrombosis:
Change in vessel wall
Change in blood flow
Change in blood constituents
43
How does low dose Aspirin work
Low dose aspirin inhibits platelet aggregation, so this can be prescribed to reduce the risk of thrombosis.
44
Define Embolism
the process of a solid mass in the blood being carried through the circulation to a place where it gets stuck and blocks the vessel
45
define Embolus
mass of material in the vascular system able to become lodged within a vessel and block it
46
What are the common types of embolus
Usually caused by a thrombus from a blood vessel
Air
Tumour
Amniotic fluid (rare in pregnant women)
Fat (severe trauma with fractures)
47
define Ischaemia
reduction of blood flow to a tissue, reducing perfusion but not causing cell death
48
define Infarction
a reduction of blood flow to a tissue that is so reduced that it cannot even support mere maintenance of the cells in that tissue so they die
49
define End artery supply
an organ that only receives blood supply from one artery.
50
Why is end arterial supply problematic
As when a blood clot forms,the whole blood supply to that organ is cut off leading to infarction.
51
Atheroma
degeneration of the walls of the arteries caused by accumulated fatty deposits and scar tissue, and leading to restriction of the circulation and a risk of thrombosis.
52
Define Apoptosis
programmed cell death
53
Apoptosis in cancer
lack of apoptosis – mutated p53 gene producing faulty p53 protein, p53 gene important in apoptosis
54
Apoptosis in HIV
too much apoptosis – kills the antibodies in the blood so the body can’t defend itself.
55
What is apoptosis triggered by
DNA damage such as:
Single-strand break
Base alteration
Cross-linkage
56
define Necrosis
death of most or all of the cells in an organ or tissue due to disease, injury, or failure of the blood supply
57
Name 5 clinical examples of necrosis
Toxic spider venom
Frostbite
Cerebral infarction
Avascular necrosis of bone – femur has single arterial supply through the neck of the femoral head
Pancreatitis
58
define Hypertrophy
increase in size of a tissue cause by an increase in size of the constituent cells
(the size of the cell/tissue/organ increases without an increase in the number of cells)
59
define Hyperplasia
increase in size of a tissue caused by an increase in number of the constituent cells
60
define Atrophy
decrease in size of a tissue caused by a decrease in number of the constituent cells or a decrease in their size
61
define Metaplasia
change in differentiation of a cell from one fully-differentiated type to a different fully-differentiated type
62
define Dysplasia
imprecise term for the morphological changes seen in cells in the progression to becoming cancer
63
What change caused by cell division causes ageing
telomeres get shorter after each cell division – limiting the amount of division that can occur (hence ageing occurs)
64
What is Dermal elastosis
Accumulation of abnormal elastic in the dermis of the skin
Result of prolonged/ excessive sun exposure – photoaging
UV light causes protein cross-linking
65
What is Cataracts
Result of the formation of opaque proteins within the lens which usually also results in a loss of lens elasticity
UV-B light causes protein cross-linking
66
Define Carcinogenesis
the transformation of normal cells to neoplastic cells through permanent genetic alterations or mutations
67
What is the difference between oncogenesis and carcinogenesis
Oncogenesis applies to benign and malignant tumors, carcinogenesis applies only to malignant
68
what are carcinogens?
Agents known or suspected to cause cancer, they act on DNA so are Mutagenic
69
Define Oncogens
Agents known or suspected to cause tumours
70
Give 2 examples of occupational risks for cancer
Scrotal cancer – increased incidence in chimney sweeps
Bladder cancer – increased incidence in aniline dye and rubber industries
71
what are the 5 classes of Carcinogens
Chemical
Viral
Ionising and non-ionising radiation
Hormones, parasites and mycotoxins
Miscellaneous
72
What are pro-carcinogens and ultimate carcinogens
Chemical carcinogens pre and post metabolic conversion
most chemical carcinogens require metabolic conversions
73
What are three examples of groups affected by radiation carcinogens
Skin cancer in radiographers
Lung cancer in uranium miners
Thyroid cancer in Ukrainian children
74
What are the 5 classes of Host factors for cancer
Race
Diet
Constitutional factors
Premalignant conditions
Transplacental exposure
75
What % of cancer risks are inherited
15%
76
give 2 examples of how race affect cancer risk
Decreased skin cancer in black people (melanin)
Increased oral cancer in India, SE Asia (reverse smoking)
77
How do constitutional factors affect cancer risk
Age – incidence increases with age
Gender – breast cancer F:M = 200 (more common in women)
78
Define tumour
any abnormal swelling e.g. neoplasm, inflammation, hypertrophy, hyperplasia
79
Define Neoplasm
a lesion resulting from the autonomous or relatively autonomous abnormal growth of cells which persists after the initiating stimulus has been removed – a new growth.
(all neoplasms are tumours but not all neoplasms are tumours)
80
What are the 3 classifications of Neoplasms
Benign
Borderline
Malignant
81
How can Neoplasms cause morbidity and mortality
Pressure on adjacent structures
Obstruct flow
Production of hormones
Transformation to malignant neoplasm
Anxiety
82
How can malignant neoplasms cause morbidity and mortality
Destruction of adjacent tissue
Metastases
Blood loss from ulcers
Obstruction of flow
Hormone production
Paraneoplastic effects
Anxiety and pain
83
define Papilloma
benign tumour of non-glandular, non-secretory epithelium
84
Define Adenoma
benign tumour of glandular or secretory epithelium
85
Define Carcinoma
malignant tumour of epithelial cells
86
4 examples of how benign connective tissue neoplasms named
Lipoma – adipocytes
Chondroma – cartilage
Osteoma – bone
Angioma – vascular
87
What are solid neoplasms composed of
Solid Neoplasms are composed of neoplastic cells and stroma (supporting network of cells)
88
Give 2 examples of Benign neoplasms
Fibroid
Tubulovillous adenoma
89
give 2 examples of Malignant neoplasms
Prostate cancer
Squamous cell carcinoma
90
define Carcinoma in situ
a malignant epithelial neoplasm that has not yet invaded through the original basement membrane
91
define Invasive carcinoma
a carcinoma that has breached the basement membrane – it can now spread elsewhere
92
define Micro-invasive carcinoma
has breached the basement membrane but hasn’t invaded very far away from the original carcinoma
93
what is the process of invasion
neoplastic cells spread directly through tissue and gain access to blood vessels and lymphatic channels
94
What is invasion dependent on
decreased cellular adhesion,
abnormal cellular motility
the production of enzymes with a lytic effect on the surrounding tissues
95
What is metastasis
Process by which a malignant tumour spreads from its primary site to produce secondary tumours at distant sites
96
what routes can metastasis occur through
via blood vessels, lymphatics, across body cavities, along nerves or as a result of direct implantation of neoplastic cells during a surgical procedure
97
What are the 7 steps of the metastatic cascade
Detachment
Invasion
Intravasation
Evasion of host defences
Arrest
Extravasation
Vascularisation
98
What is the maximum diameter a tumour can grow before it requires vascularisation
1mm
99
Name two angiogenesis promoters
Vascular endothelial growth factors
Basic fibroblast growth factor
100
Name 3 types of angiogenesis inhibitors
Angiostatin, endostatin, vasculostatin
101
What is Haematogenous metastsis
The route of metastasis by the blood stream – forms secondary tumours in organs perfused by blood that has drained from a tumour
102
What is lymphatic metastasis
the route of metastasis by lymph channels – form secondary tumours in the regional lymph nodes
103
What is Trans-coelomic metastasis
rputeof tumour metastasis across cavities such as pericardial and peritoneal cavities
104
Which tumours commonly metastasise to the lung
sarcomas and any common cancers
105
Which tumours commonly metastasise to the liver
colon, stomach, pancreas, and carcinoid tumours of intestine
106
which tumours commonly metastasise to bone
prostate, breast, thyroid, lung and kidney
107
Name two treatment options for breast cancer
Anti-oestrogen drugs
Herceptin
108
Why and when to use anti-oestrogen drugs for breast cancer
Giving drugs that block the oestrogen receptors on the cancer cells which inhibits their growth. The tumours are stained in the lab for oestrogen receptors so that oncologists can decide whether a breast cancer is likely to respond to anti-oestrogen therapy.
109
why use herceptin for breast cancer
Herceptin is a drug that binds to the Her2 protein on the outside of the cell membrane.
Tumours overexpress a growth factor receptor on their cell surface called Her2 protein. This is coded for by the HER2 gene.
This drug binding to the protein on the surface of the cancer cells reduces their rate of growth
110
What is the main requirement of the immune system
to discriminate self from non-self
111
What are the 2 categories of immunity
Innate immunity
Adaptive immunity
112
What is innate immunity
non-specific, instinctive, does not depend on lymphocytes
113
What is adaptive immunity
specific ‘acquired’ immunity, requires lymphocytes, antibodies
Is made up of cells and soluble proteins (humoral)
114
What is the stem cell that every blood cell in the body originates from
Haematopoietic pluripotent stem cell (haemocytoblast)
115
What are Polymorphonuclear leukocytes
Cells with multi-lobed nuclei-
neutrophils, eosinophils and basophils
116
What are Mononuclear leukocytes
Cells with single-lobed nuclei-
monocytes (kidney shaped nuclei), T-cells and B-cells (lymphocytes)
117
What is the role of Neutrophils in immunity
Plays an important role in innate immunity (phagocytosis)
2 main intracellular granules
Primary lysosomes – can kill microbes by secreting toxic substances
Secondary granules- may have regulatory functions outside the cell
118
Role of Monocytes in immunity
Plays an important role in innate AND adaptive immunity (phagocytosis and Ag presentation)
Differentiate into macrophages in the tissues
Main role – remove anything foreign (microbes) or dead
119
Role of Macrophages in immunity
Play important role in innate and adaptive immunity (phagocytosis and Ag presentation)
Reside in tissues, lifespan – months/years e.g. Kupffer cells – liver, microglia – brain
Most often first line of non-self recognition
Main role – remove foreign (microbes) and self (dead/tumour cells)
Present Ag to T-cells
120
Role of Eosinophil in immunity
Mainly associated with parasitic infections and allergic reactions
Lifespan 8-12 days
Granules stain for acidic dyes (eosin)
Activates neutrophils, induces histamine release from mast cells and provokes bronchospasm
121
Role of basophil in immunity
Mainly involved in immunity to parasitic infections and allergic reactions
Lifespan 2 days
Granules stain for basic dyes
Very similar to mast cells
Binding of IgE to receptor causes de-granulation releasing histamine – main cause of allergic reactions
122
role of mast cells in immunity
Only in tissues (precursor in blood)
Very similar to basophils
Binding to IgE to receptor causes de-granulation releasing histamine – main cause of allergic reactions
123
role of T-lymphocytes in immunity
Play major role in adaptive immunity
Lifespan hours-years
Mature in thymus
Found in blood, lymph nodes and spleen
Recognise peptide Ag displayed presenting cells (APC)
124
What are the 4 types of T-cell and their roles
T helper 1 (CD4 – help immune response intracellular pathogens)
T helper 2 (CD4 – help produce antibodies extracellular pathogens)
Cytotoxic T cell (CD8 – can kill cells directly)
T regulator – regulate immune responses
125
Role of B lymphocytes in immunity
Play major role in adaptive immunity
Lifespan hours – years
Mature in bone marrow
Recognise Ag displayed by antigen presenting cells (APC)
Differentiate into plasma cells that make antibodies
Found in blood, lymph nodes and spleen
126
Role of Natural killer cells
Part of innate immune response
Account for 15% of lymphocytes
Found in spleen, tissues
They recognise and kill by apoptosis;
Virus infected cells
Tumours cells
127
What are the 4 soluble factors involved in immunity
Complement, antibodies, cytokines and chemokines
128
What are complement factors and how do they work
Classical – Ab bound to microbe
Alternative – C binds to microbe
Mode of action
Direct lysis
Attract more leukocytes to site of infection (chemotaxis)
Coat invading organisms (opsonisation)
129
What is an antibody
protein produced in response to an antigen. It can only bind with the antigen that induced its formation – i.e. specificity.
130
What are immunoglobulins (antibodies) and what are the 5 classes
Ig’s are soluble glycoproteins, with distinct classes : G, A, M, D, E
131
What is IgG
Predominant in human serum, 70-75% of total Ig in serum
Crosses placenta
132
What is IgA
Accounts for 15% of Ig in serum
Predominant Ig in mucous secretions such as saliva, milk and bronchiolar secretions.
133
What is IgM
Accounts for 10% of Ig in serum
Mainly found in blood (they’re big so they can’t cross the endothelium)
Mainly primary response, initial contact with Ag
134
What is IgD
Accounts for 1% of Ig in serum
A transmembrane monomeric form is present on mature B cells
135
What is IgE
Accounts for ~0.05% of Ig in serum
Basophils and mast cells express an IgE-specific receptor that has high affinity for IgE – binding triggers release of histamine
Associated with allergic response and defence against parasitic infections
136
Define Antigen
a molecule that reacts with preformed antibody and specific receptors on T and B cells.
137
Define Epitope
the part of the antigen that binds to the antibody/ receptor binding site
138
Define Affinity
measure of binding strength between an epitope and an antibody binding site. The higher the affinity the better.
139
define cytokines
proteins secreted by immune and non-immune cells. Substances produced by one cell that influence the behaviour of another, thus effecting intercellular communication.
140
What are the 4 types of Cytokines
Interferons (IFN)
Interleukins (IL)
Colony stimulating factors (CSF)
Tumour necrosis factors
141
What is the role of interferons
induce a state of antiviral resistance in uninfected cells and limit the spread of viral infection
142
What is the role of interleukins
produced by many cells, over 30 types.
Can cause cells to divide, to differentiate and to secrete factors
143
What is the role of colony stimulating factors
Involved in directing the division and differentiation on bone marrow stem cells – precursors of leukocytes
144
What is the role of tumour necrosis factors
Mediate inflammation and cytotoxic reactions
145
What are Chemokines
Group of approx. 40 proteins that direct movement of leukocytes from the blood stream into the tissues or lymph organs by binding to specific receptors on cells.
They attract leukocytes to sites of infection/inflammation – like magnets
146
What is the role of the Skin in innate immunity
is an anatomical barrier
Sebum (skin secretions)
Intact skin – prevents penetration, prevents growth
147
What is the role of mucous membranes in innate immunity
physical barrier
Saliva
Tears – lysozyme in tears and other secretions
Low pH and commensals of vagina
Mucous secretions
Mucous – entrapment
Cilia – beating removes microbes
Commensal colonies – attachment, nutrients
148
Define commensals
those type of microbes that reside on either surface of the body or at mucosa without harming human health.
149
Physiological barrier
High body temperature
Fever response inhibits micro-organism growth
pH changes
Gastric acidity
150
Define Extravasation
a discharge or escape, as of blood, from a vessel into the tissues. Usually lymph from blood into tissues
151
Define opsonisation
the coating of pathogens with antibodies in order to increase their susceptibility to ingestion by phagocytes.
152
What is C3b
Part of Complement component 3, is an important molecule in opsonisation
153
What is the major histocompatibility (MHC)
a group of genes that encode proteins on the cell surface that have an important role in immune response. they display self or non-self proteins.
154
What are the three MHC classes
MHC I- glycoproteins on all nucleated cells
MHC II- glycoproteins only on APC
MHC III- code for secreted proteins- not fully understood
155
What is an APC
Antigen presenting cell works in conjugation with MHC II to present antigens to T cells
156
Role of MHC I
Intrinsic (intracellular) – present intracellular proteins on surface to alert immune system, interacts with cytotoxic T (CD8) cells
157
Role of MHC II
Presents extracellular proteins to T helper (CD4) cells, initiates antigen specific immune response
158
What is T cell selections
T cells that recognise self are killed in the foetal thymus as they mature
159
Summarise B cell activation
B cells become activated upon binding with an antigen. These then go to the lymph nodes where clonal expansion takes place with the cells differentiating into plasma cells. These secrete Ab (usually IgM) which later turn into IgG. B cells divide – clonal expansion and differentiate into plasma cells and memory B cells. Re-stimulation of memory B cells lead to secondary response.
160
What do T helper (CD4) cells do
help coordinate the immune response by stimulating other immune cells, such as macrophages, B lymphocytes (B cells), and CD8 T lymphocytes (CD8 cells), to fight infection.
161
What do cytotoxic T (CD8) cells do
kill virus-infected cells and produce antiviral cytokines such as interferon gamma.
162
What are Pattern Recognition Receptors (PRRs)
proteins capable of recognizing molecules frequently found in pathogens. these are :
Pathogen-Associated Molecular Patterns-PAMPs
or Damage-Associated Molecular Patterns-DAMPs which are molecules released by damaged cells
163
What are the 2 types of PRRs
Secreted and circulating PRRs
Cell-associated PRRs (more traditional receptors)
164
What are Secreted and circulating PRRs
Antimicrobial peptides secreted in lining fluids from epithelia
Lectins and collectins (carbohydrate-containing proteins that bind carbohydrates or lipids in microbe walls. Activate complement, improve phagocytosis.
165
What are Cell-associated PRRs
Receptors that are present on the cell membrane or in the cytosol of the cells
Recognise a broad range of molecular patterns
TLRs are the main family (toll-like receptors)
166
Role of TLRs
a class of pattern recognition receptors (PRRs) that initiate the innate immune response by sensing conserved molecular patterns for early immune recognition of a pathogen
167
What are the 3 types of vaccines
whole killed, toxoids, live attenuated
168
Define passive immunisation
Passive immunity is a short-term immunity which results from the introduction of antibodies from another person or animal.
169
What are the pros and cons of Passive immunisation
Advantages:
Gives immediate protection
Effective in immunocompromised patients
Disadvantages:
Short-lived
Possible transfer of pathogens
170
Define Vaccines
antigenic substance prepared from the causative agent of a disease
171
What are whole killed vaccines and their limitations
These vaccines do not cause infection but the antigens contained in it induce an immune response which protects against infection.
The organisms must be grown to high titre in vitro
Whole pathogens often cause excessive reactogenicity
Usually need at least 2 vaccinations
172
What are live attenuated vaccines
The organisms replicate within the host, and induce an immune response which is protective against the wild-type organism
173
What are toxoids
Non-living vaccines can also be cell-free toxoids (inactivated toxins
174
What are the pros and cons of Live attenuated vaccines
Advantages:
Lower doses are required, so the scale of in vitro growth needed is lower
Immune response more closely mimics that following real infection
Route of administration may be more favourable
Fewer doses may be required
Limitations:
Often impossible to balance attenuation and immunogenicity
Reversion to virulence
Transmissibility
Live vaccines may not be so attenuated in immunocompromised
175
What are the stages of vaccination
Engage the innate immune system
Danger signals that activate the immune system, triggers such as molecular fingerprints of infection – PAMPs (pathogen associated molecular patterns)
Engage TLR receptors
Activate specialist APC
Engage the adaptive immune system
Generate memory T and B cells
Activate T cell help
176
General features for Tumours in immunity
Tumours express antigens that are recognised as foreign by the immune system of the tumour-bearing host
Immune responses frequently fail to prevent growth of tumours
The immune system can be activated by external stimuli to effectively kill tumour cells and eradicate tumours
177
Define immuno-surveillance
immune system can recognise and destroy nascent transformed cells, normal control
178
Define Cancer immunoediting
Immune system can kill and also induce changes in the tumour resulting in tumour escape and recurrence.
179
What are the 2 types of tumour antigens
Tumour specific antigens (TSA)
Tumour associated antigens (TAA)
180
What are the features of Tumour specific antigens (TSA)
Are only found on tumours
As a result of point mutations or gene rearrangement
Derive from viral antigens
181
What are the features of Tumour associated antigens (TAA)
Found on both normal and tumour cells, but are overexpressed on cancer cells
Developmental antigens which become de-repressed
Differentiation antigens are tissue specific
Altered modification of a protein could be an antigen
182
Define Tumour escape
immune responses change tumours such that tumours will no longer be seen by the immune system.
183
Define immune evasion
tumours change the immune responses by promoting immune suppressor cells.
184
Define Cancer immunotherapy
induce an immune response against the tumour that would discriminate between the tumour and normal cells
185
What are the types of Immunotherapy vaccines
Killed tumour vaccine
Purified tumour antigens
Professional APC-based vaccines
Cytokine – enhanced vaccines
DNA vaccines
Viral vectors (augmentation of host immunity to tumours with cytokines and costimulators)
186
What is tumour hypoxia
Hypoxia is a prominent feature of malignant tumours
Inability of the blood supply to keep up with growing tumour cells
Hypoxic tumour cells adapt to low oxygen
187
Why does tumour hypoxia = poor patient prognosis
Stimulates new vessel growth
Suppressed immune system
Resistant to radio and chemotherapy
Increased tumour hypoxia after therapy
188
What is a synergic drug interaction
interaction of drugs such that the total effect is greater than the sum of the individual effects (1+1>2)
189
What is an antagonistic drug interaction
an antagonist is a substance that acts against and blocks an action (2 drugs opposed to each other) (1+1=0)
190
What is a summation drug interaction
different drugs used together to have the same effect as a single drug would (1+1=1)
191
What is a potentiation drug interaction
enhancement of one drug by another so that the combined effect is greater than the sum of each one alone (1+1=1+1.5)
192
Define Pharmacodynamics
the effect the drug has on the human body
193
Define pharmacokinetics
what the body does with the drug (the disposition of a compound within an organism)
194
What are risk factors of a drug need to be considered for administration
Narrow therapeutic index
Steep dose/response curve
Saturable metabolism
195
What is ADME
the mechanisms of pharmokinesis:
Absorption, Distribution, Metabolism, Excretion
196
What factors affect absorption (pharmacology)
Motility – if the gut has slowed digestion, the drugs won’t work as well (oral contraceptive pill and antibiotics is the most common interaction)
Acidity – pH and pKa interactions.
Solubility
Complex formation
197
What are the factors affecting distribution (pharmacology)
Drugs can go into the proteins, other tissues or the effect site
Protein binding
If you give 2 highly protein bound drugs, they will make each other strong and increase their effect so you always make sure you know what drugs the patient has taken before giving them new drugs
198
What are the factors affecting metabolism (pharmacology)
CYP450 proteins- these metabolise many substrates
inhibition- Drug A blocks metabolism of drug B, leaving more free drug B in the plasma so it has an increased effect
induction- Drug C induced CYP450 isoenzyme leading to increased metabolism of drug D so it has a decreased effect
199
What affects excretion (pharmacology)
Renal:
-pH dependant
-Weak bases – cleared faster if urine acidic
-Weak acids – cleared faster if urine alkali
Billary (minor)
199
What are the receptor based pharmacodynamic mechanism types
Agonists
Partial agonists
Antagonists:
-Competitive
-Non-competitive
200
What is signal transduction
the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events
201
What are 2 examples of drug interactions to be aware of
Warfarin – lots of interactions – enzyme induction
Acute kidney injury – NSAIDs, ACEi
202
Define Drug
a medicine or other substance which has a physiological effect when ingested or otherwise introduced into the body
203
Define pharmacology
the branch of medicine concerned with the uses, effects and modes of action of drugs
204
What are the 4 major drug target proteins
Receptors
Enzymes
Transporters
Ion channels
205
define receptor
a component of a cell that interacts with a specific ligand and initiates a change of biochemical events leading to the ligands observed effects.
206
What conditions involve an imbalance of chemicals/receptors
Chemicals
Allergy; increased histamine
Parkinson’s; reduced dopamine
Receptors
Myasthenia gravis; loss of ACh receptors
Mastocytosis; increased c-kit receptor
207
What are the 4 classes of receptor
ligand-gated ion channels
G-protein coupled receptors
kinase-linked receptors
cytosolic/ nuclear receptors
208
define ligand
a molecule that binds to another (usually larger) molecule
209
Define Agonist
a compound that binds to a receptor and activates it
210
define antagonist
a compound that reduces the effect of an agonist
211
What are the two categories of cholinergic receptors
nicotinic and muscarinic
212
What are the antagonist and receptor for muscarine
Atropine and mAChR
213
What are the antagonist and receptor for nicotine
Curare
nAChR
214
define affinity
describes how well a ligand binds to the receptor
215
define Efficacy
describes how well a ligand activates the receptor
216
Signal transduction
a basic process involving the conversion of a signal from outside the cell to a functional change within the cell
217
what is allosteric modulation
When an allosteric ligand binds to a different site on the molecule and prevents the signal from being transmitted.
218
How do ACE inhibitors work
RAAS increases blood pressure by increasing the amount of salt and water the body retains.
Inhibiting ACE reduces angiotensin II production, which causes a reduction in blood pressure.
219
What are the 3 main types of protein ports
Uniporters – use energy from ATP to pull molecules in
Symporters – use the movement in of one molecule to pull in another molecule against a concentration gradient
Antiporters – one substance moves against its gradient, using energy from the second substance (mostly Na+, K+ or H+) moving down its gradient
220
221
What are CYPs
(e.g. cyP450) are the major enzymes involved in drug metabolism (75%)
Most drugs undergo deactivation by CYPs, either directly or by facilitated excretion from the body.
222
define druggability
the ability of a protein target to bind small molecules with high affinity (sometimes called ligandability).
223
What are 8 sources for drug development
Medicines from plants
Inorganic elements
Organic molecules
Bacteria/fungi/moulds
Stereoisomers
Immunotherapy antibodies
Medicines from animals
Gene therapy
224
What are 6 examples of recombinant proteins in clinical use
Insulin
Erythropoietin
Growth hormone
Interleukin 2
Gamma interferom
Interleukin 1 receptor
225
Describe gene therapy
Gene therapy consists of a recombinant nucleic acid used in or administered to a human being with a view to regulating, replacing, adding or deleting a genetic sequence
Its effect relates directly to the recombinant nucleic acid sequence it contains or to the product of genetic expression of this sequence
226
What is rational drug design
The process of finding new medications based on the knowledge of a biological target
227
define adherence
the extent to which the patient’s actions match agreed recommendations
228
Necessity beliefs
perceptions of personal need for treatment
-concerns about a range of potential adverse consequences
229
define Pharmacokinetics
the action of the body on the drug (ADME)
230
What is drug ionization
property of weak acid or base drugs- pH of environment changes absorption through drugs changing between ionized and unionized form
231
How does drug structure affect absorption
Drugs need to be lipid soluble to be absorbed from gut
Some drugs unstable at low pH or in presence of digestive enzymes so have to be given by alternative route
232
How does drug formulation affect absorption
The capsule/ tablet must disintegrate and dissolve to be absorbed
Some formulated to dissolve slowly or have a coating that is resistant to the acidity of the stomach
233
How does gastric emptying affect drug absorption
Rate of gastric emptying determines how soon a drug taken orally is delivered to small intestine
Can be slowed (food/drugs) or sped up (gastric surgery)
234
What is first pass metabolism for oral administration and the 4 barriers
any loss of the administered material by transmucosal or hepatic means after absorption and before reaching the systemic circulation,
Intestinal lumen
Intestinal wall
Liver
Lungs
235
What are 4 reasons to use intradermal or subcutaneous methods
Avoids barrier of stratum corneum
Mainly limited by blood flow
Small volume can be given
Use for local effect or to deliberately limit rate of absorption
236
What affects IM absorption and why use it
Depends on blood flow and water solubility
Increase in either enhances removal of drug from injection site
Can make a depot injection by incorporating drug into lipophilic formulation which releases drug over days or weeks
237
What affects inhalational absorption and why use it
Large SA and blood flow but limited by risks of toxicity to alveoli and delivery of non-volatile drugs
Largely restricted to volatiles such as general anesthetics and locally acting drugs such as bronchodilators in asthma
Asthma drugs non-volatile so given as aerosol or dry powder
238
What is protein binding and what affects it
Many drugs can bind to plasma or tissue proteins
This may be reversible or irreversible
The most common reversible binding occurs with the plasma protein albumin
Binding lowers the free concentration of drug and can act as a depot releasing the bound drug when the plasma concentration drops through redistribution or elimination
Some drugs bind irreversibly and cannot re-enter the circulation and is equivalent to elimination
239
the relationship between drug structure, the brain and placenta
Lipid soluble drugs easily pass from blood to brain
The brain does little metabolizing and drugs are removed by diffusion into plasma, active transport in the choroid plexus or elimination in the CSF
Lipid soluble drugs readily cross placenta
Large molecules do not cross placenta
Foetal liver has low levels of drug metabolizing enzymes, so relies on maternal elimination
240
Define elimination
The removal of a drugs activity from the body, either by metabolism to an inactive form or by excretion
241
What is drug metabolism needed for
Necessary for the elimination of lipid soluble drugs
They are converted to water soluble products that are readily removed in the urine
242
What is Phase 1 metabolism
these reactions involve the transformation of the drug to a more polar metabolite
done by unmasking or adding a functional group
oxidations are the commonest reactions catalyzed by CP450
243
What is phase 2 metabolism
involves the 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
244
What methods of drug excretion are there
Fluids – important for low molecular weight polar compounds (urine, bile, sweat, tears, breast milk)
Urine excretion: Total excretion = glomerular filtration + tubular secretion – reabsorption
Solids – faecal elimination
Gases – expired air important for volatiles
245
What is first order drug kinetics
Concentration declines exponentially
246
What is zero order drug elimination
occurs when the metabolising enzyme is saturated, the rate of drug elimination is constant
247
What is Bioavailability
Fraction of the administered drug that reaches the systemic circulation unaltered (F)
F=1 for IV
for any drugs with first pass metabolism F<1
248
Define distribution
Rate and extent of movement of a drug into tissues from blood
249
What factor affects rate of distribution for water soluble drugs
rate of passage across membranes
250
What factor affects rate of distribution of lipid soluble drugs
blood flow to tissues that accumulate the drug
251
What is volume of distribution
the total amount of drug in body (dose)/ plasma concentration
252
Define clearance
the volume of blood or plasma cleared of drug per unit time
253
What is the relationship between elimination and volume of distribution
inversely proportional
k= Clearance/ Vd
254
What is steady state
the balance between drug input and elimination (Css)
255
Give an example of the difference in doseage dictated by route of administration
50% of oral morphine is metabolized by the first pass metabolism. Halve the dose if given IM/ IV
256
Mechanism of opioids
use the existing pain modulation system
The opioid receptors are coupled to G1 proteins and the actions of the opioids are mainly inhibitory. decrease neuronal excitability.
257
Define drug potency
whether a drug is ‘strong’ or ‘weak’ relates to how well the drug binds to the receptor, the binding affinity.
258
define efficacy
the concept of full or partial agonists
259
define tolerance
down regulation of the receptors with prolonged use. Need higher doses to achieve the same effect
260
What is the timeframe of opioid withdrawal
starts within 24 hours, lasts about 72 hours
261
What are some side effects of opioids
Respiratory depression
Sedation
Nausea and vomiting
Constipation
Itching
Immune suppression
Endocrine effects
262
Why do opioids have side effects
Opioid receptors exist outside the pain system e.g. digestive tract, respiratory control centre
normally delivered systemically so activate these
263
How is morphine removed from the body
Morphine is metabolized to morphine 6 glucuronide which is more potent than morphine and is renally excreted.
264
Why does renal function affect morphine doseage
metabolised and cleared by the kidney
With normal renal function this is cleared quickly
In renal failure it will build up and may cause respiratory depression
Be careful in patients with <30% renal function (creatinine clearance <30). Reduce dose and timing interval
265
What is cholinergic and adrenergic pharmacology responsible for
Control of blood pressure
Control of heart rate
Anaesthetic agents
Regulation of airway tone
Pressures in the eye
Control of GI function
266
What is the structure of the parasympathetic nervous system
Cranial nerves like the oculomotor nerve, facial nerve and vagus nerve carry signals to the body
A further sacral outflow innervates the pelvis
Short post-synaptic nerve fibres reach the targets and release acetylcholine (ACh), which acts on muscarinic receptors of various subtypes
267
What is the structure of the sympathetic nervous system
Regulates the fight-and-flight response
Nerve fibres originating in the spinal cord terminate in ganglia near the cord, then send out long nerve fibres to blood vessels, muscles etc.
They release noradrenaline which activates adrenergic receptors, of which there are two main types (alpha/ beta) with subtypes
268
what is involved with the parasympathetic and sympathetic fibres immediately out of the CNS
Parasympathetic and sympathetic fibres coming out of the CNS both release ACh, which acts on nicotinic receptors
269
What mediators and receptors are involved in post-ganglionic parasympathetic interactions
The post-ganglionic parasympathetic fibres release more acetylcholine, acting on muscarinic receptors
270
What mediators and receptors are involved in post-ganglionic sympathetic interactions
The post-ganglionic sympathetic fibres release noradrenaline, acting on alpha and beta adrenoceptors
270
What type of receptors are muscarinic receptors
G-Protein-Coupled Receptors
G proteins can activate various types of second messenger signals
271
Where are muscarinic receptors M1-5 located
M1: mainly in the brain
M2: mainly in the heart. (their activation slows the heart, so we can block these)
M3: glandular and smooth muscle. (cause bronchoconstriction, sweating, salivary gland secretion
M4/5: mainly in the CNS
272
What are some side effects of anticholinergic drugs
In the brain, anticholinergics worsen memory and may cause confusion
Peripherally, may get constipation, drying of the mouth, blurring of the vision, worsening of glaucoma
273
How do alpha 1 agonists act
Alpha 1 activation causes vasoconstriction, particularly in the skin and splanchnic beds: less so in brain, lung, heart
274
What receptor does adrenaline act on
Alpha 1, causes vasoconstriction
275
What are the reponses of blood pressure to alpha1/2 agonists
Alpha 1 activators raise blood pressure
Alpha 2 activators lower blood pressure
276
What do agonists of Beta 1 receptors do
Beta 1 activation will increase heart rate and chronotropic effects, and may increase risk of arrhythmias
277
What do agonists of Beta 2 receptors do
Beta 2 activation is life saving in asthma, causes bronchodilation, relaxing of smooth muscle
278
What do beta blockers do
Lower blood pressure (reduction in cardiac output reduction in central sympathetic outflow activity)
279
What are 5 clinical indications for allergy
Epithelial – eczema, itching, reddening
Excessive mucus production
Airway constriction
Abdominal bloating, vomiting, diarrhoea
Anaphylaxis
280
Define allergy
an abnormal response to harmless foreign material
281
What 4 immune cells are involved in allergy
Mast, eosinophil, lymphocytes, dendritic
282
what 3 non-immune cells are involved in allergy
Smooth muscle, fibroblasts, epithelia
283
What are 4 mediators in allergy
Cytokines, chemokines, lipids, small molecules
284
What process is required for IgE receptors to cause signalling
clustering
285
Which cells express low affinity IgE recpetors
B cells, T cells, monocytes, eosinophils, platelets, neutrophils
286
What is the function of IgE receptors
Regulation of IgE synthesis
Triggering of cytokine release by monocytes
trigger Antigen presentation by cells
287
Which cells express high affinity IgE receptors
Eosinophils, mast cells and basophils
288
What are 3 indirect activators of mast cells and what mediates this
Allergens e.g. wasp venom, pollen
Bacterial/viral antigens
Phagocytosis of enterobacteria
mediated by IgE
289
What are direct activators of mast cells
Cold/mechanical deformation
Aspirin, preservatives, latex
290
What are adverse drug reactions
unwanted or harmful reactions following the administration of drugs or combination of drugs under normal conditions of use and is suspected to be related to the drug
291
What are side effects
an unintended effect of a drug related to its pharmacological properties and can include unexpected benefits of treatment
292
Give an example of an adverse drug reaction
Beta blockers
Bradycardia and heart block are primary adverse effects
Bronchospasm is a secondary pharmacological adverse effect
293
What is the classification model for adverse drug reactions
Rawlins Thompson classification
294
What is a type A ADR
Type A – (augmented pharmacological) – predictable, dose dependent, common
295
What is a type B ADR
Type B – (bizarre or idiosyncratic) – not predictable and not dose dependent
296
What is a type C ADR
Type C – (chronic) –steroids causing osteoporosis
297
What is a Type D ADR
Type D – (delayed) – malignancies after immunosuppression
298
What is a type E ADR
Type E – (end of treatment) – occur after abrupt drug withdrawal
299
What is a type F ADR
Type F – (failure of therapy) – failure of oral contraceptive pill in presence of enzyme inducer
300
What are 3 causes of ADRs
Pharmaceutical variation
Receptor abnormality
Drug-drug interactions
301
What are 4 signs of an ADR
Symptoms soon after a new drug is started
Symptoms after a dosage increase
Symptoms disappear when the drug is stopped
Symptoms reappear when the drug is restarted
302
Describe the yellow card system
The first ADR reporting scheme
Collects spontaneous reports
Acts as an ‘early warning system’ for identification of previously unrecognised reactions
Provides information, about factors which predispose patients ADRs
Continual safety monitoring of a product throughout its life span as a therapeutic agent
303
What are the 4 critical pieces of information to include on a yellow card
Suspected drug
Suspect reaction
Patient details
Reporter details
304
What is type 1 hypersensitivity
Type 1 – IgE mediated hypersensitivity
305
What is the mechanism of type 1 hypersensitivity
Prior exposure to the antigen
IgE becomes attached to mast cells or leukocytes, expressed as cell surface receptors
Re-exposure causes mast cell degranulation and release of pharmacologically active substances
306
What is type 2 hypersensitivity
Type 2 – IgG mediated cytotoxicity
307
What is the mechanism of type 2 hypersensitivity
Antibody dependent cytotoxicity
Drug or metabolite combines with a protein
Body treats it as a foreign protein and forms antibodies
Antibodies combine with the antigen and complement activation damages the cells
308
What is type 3 hypersensitivity
Type 3 – immune complex deposition
309
What is the mechanism of type 3 hypersensitivity
Immune complex mediated
Small blood vessels are damaged or blocked
Leucocytes attracted to the site of reaction release pharmacologically active substances leading to an inflammatory process
310
What is type 4 hypersensitivity
Type 4 – T cell mediated
311
What is the mechanism of type 4 hypersensitivity
Lymphocyte mediated
Antigen specific receptors develop on T-lymphocytes
Subsequent administration leads to local or tissue allergic reactions
312
Define anaphylaxis
an acute allergic reaction to an antigen to which the body has become hypersensitive
313
What are the main features of anaphylaxis
Exposure to drug, immediate rapid onset rash
Swelling of lips, face, oedema, central cyanosis
Hypotension
Cardiac arrest
314
What is the management of anaphylaxis
Commence basic life support
Adrenaline – IM 500µg
High flow oxygen
315
How does adrenaline work
Vasoconstriction – increase in peripheral vascular resistance, increased BP and coronary perfusion
Stimulation of beta1-adrenoceptors positive ionotropic and chronotropic effects on the heart
Reduces oedema and bronchodilates via beta2-adrenoceptors
316
Define pathogen
Organism that causes or is capable of causing disease
317
define commensal
Organism which colonises the host but causes no disease in normal circumstances
318
define opportunist pathogen
Microbe that only causes disease if host defenses are compromised
319
Define virulence/pathogenicity
The degree to which a given organism is pathogenic
320
Define asymptomatic carriage
When a pathogen is carried harmlessly at a tissue site where it causes no disease
321
What are the outcomes of the gram stain
positive= purple
negative= pink
322
What is a coccus
Ball shaped bacteria
323
what is the apperance streptococcus bacteria
chain of cocci
324
What is the appearance of staphylococcus bacteria
cluster of cocci
325
What is the appearance of diplococcus bacteria
pairs of cocci
326
What is a bacillus
rod shaped bacteria
327
What is a vibrio
curved rod shaped bacteria
328
What is a spirochaete
Spiral rod shaped bacteria
329
What is the structure of gram negative bacteria
has 2 membranes – an inner and outer membrane, which are separated by lipoprotein, periplasmic space and peptidoglycan
330
What is a bacterial endotoxin
component of the outer membrane of bacteria, e.g. lipopolysaccharide in gram negative bacteria
331
What is a bacterial exotoxin
secreted proteins of gram positive and gram negative bacteria
332
What is the structure of gram positive bacteria
only an inner membrane, surrounded by thick layer of peptidoglycan
333
What are the two methods of genetic variation in bacteria
Mutation
Gene transfer
334
What are the 3 mechanisms of gene mutation in bacteria
Base substitution
Deletion
Transfer
335
What are the 3 mechanisms of gene transfer in bacteria
Transformation e.g. plasmid
Transduction e.g. via phage
Conjugation e.g. via sex pilus
336
What is the process of gram staining
Apply a primary stain such as crystal violet (purple) to heat fixed bacteria
Add iodide which binds to crystal violet and helps fix it to the cell wall
Decolourise with ethanol or acetone
Counterstain with safranin (pink)
337
What is the purpose of the coagulase test
Distinguishes S.aureus from other staphylococci – coagulase positive
338
What are the three outcomes of the haemolytic bacteria classification
alpha, beta, gamma
339
What is alpha haemolysis
haemolysis causing by production of hydrogen peroxide oxidising haemoglobin – the agar appears green
340
What is Beta haemolysis
complete haemolysis results because of lysis of red blood cells by haemolysis such as Streptolysin O produced by S.pyogenes - so clear agar
341
What is gamma haemolysis
implies no haemolysis
342
What is the oxidase test
Tests if micro-organism contains a cytochrome oxidase – implies organism able to use oxygen as the terminal electron acceptor
343
What are 6 important examples of gram positive bacteria
Staphylococcus Aureus, S.epidermis, S.pyogenes, S.pneumoniae, viridans streptococci, C.diphtheriae
344
What is the classification process for streptococci
gram staining
Haemolysis
Lancefield typing
Biochemical properties
345
What is lancefield grouping
a method of grouping catalyse negative, coagulase negative bacteria based on bacterial carbohydrate cell surface antigens
346
What are the main determinants of virulence
Colonization factors: adhesins, invasins, nutrient acquisition, defense
Toxins (effectors): usually secreted proteins -> damage, subversion
347
What are the 4 major groups (phyla) of gram-negative pathogens
Proteobacteria – all are rod-shaped
Bacteroids – rod-shaped
Chlamydia – round pleimorphic
Spirochaetes – spiral/ helical
348
What are the 3 groups of worms
Nematodes (roundworms)
Trematodes (flatworms, flukes)
Cestodes (tapeworms)
349
Where are the 3 types of nematodes
Intestinal – ascaris lumbricoides
Larva migrans- skin
Tissue (filaria)
350
What are the 4 types of trematodes
Blood
Liver
Lung
intestinal
351
what are the 2 types of cestodes
Non-invasive
Invasive
352
What is the pre-patent period for worms
the interval between infection and the appearance of eggs in the stool
353
What are 7 mycobacteria of clinical importance
M.tuberculosis – tuberculosis
M.leprae – leprosy
M.avium – disseminated infection in AIDS, infections in patients with chronic lung disease
M.kansasii – chronic lung infection
M.marinum – fish tank granuloma
M.ulcerans – buruli ulcer
Rapidly growing mycobacteria – skin and soft tissue infections
354
What is the microbiology of mycobacteria
Aerobic, non-spore forming, non motile bacillus
Cell wall contains high molecular weight lipids
Weakly gram-positive or colourless
Survive inside macrophages, even in low pH environment
Slow reproduction
Slow response to treatment
Slow growing
M tuberculosis generation time 15-20h vs. 1h for common bacterial pathogens
355
What are acid fast bacilli
stain used to identify organisms with wax-like, thick cell walls e.g. mycobacteria (resistant to gram stain)
356
What are 4 characteristics of viruses
Non-cellular structure – do not have membranes or any cell organelles
Consist of an outer protein coat and a strand of nucleic acid, either DNA or RNA
Come in a variety of shapes
Do not carry out metabolic reactions on their own – require the organelles and enzymes of a host to carry out such reactions
357
What are the 6 steps of viral replication
Attachment: viral and cell receptors e.g. HIV
Cell entry: only central viral core carrying the nucleic acid and some associated proteins enter host cell
Interaction with host cells: use cell materials (enzymes, amino acids, nucleotides) for their replication
Replication: may localize in nucleus, cytoplasm or both
Assembly: occurs in nucleus, in cytoplasm or at cell membrane
Release: bursting open of cell, or by leaking from the cell over a period of time
358
what are 4 ways viruses cause disease
Damage by direct destruction of host cells e.g. HIV
Damage by modification of host cell structure or function e.g. rotaviruses
Damage involving over-reactivity of the host as a response to infection e.g. hepatitis B
Damage through cell proliferation and cell immortalization e.g. HPVs
359
What are 4 main features of fungi
Eukaryotic
Chitinous cell wall
Heterotrophic- gets it food from other organisms
Move by means of growth or through the generation of spores, which are carried through air or water
360
What is the fungal cell wall made of
mannoproteins
B1,3 and B 1,6 glucan
chitin
361
What drugs target fungal cell walls
echinocandins
362
what drug targets DNA/RNA and protein synthesis in fungi
flucytosin
363
What are fungal plasma membranes made of
ergosterol (instead of cholesterol in humans)
364
What drugs target ergosterol in fungi
amphotericin
Azoles
Terbinafine
365
What is the diference between yeasts and moulds
Yeasts are small single celled organisms that divide by budding
Moulds form multicellular hyphae (branching filaments) and spores
366
What are dimorphic fungi
Some fungi exist as both yeasts and moulds switching between the two when conditions suit
367
What are features of selective toxicity in regards to treating fungal disease
Target does not exist in humans
Target is significantly different to human analogue
Drug is concentrated in organism cell with respect to humans
Increased permeability to compound
Modification of compound in organism or human cellular environment
Human cells are ‘rescued’ from toxicity by alternative metabolic pathways
368
What are 3 key features of pathogens
infectivity
virulence
invasiveness
369
What are the two types of responses to viruses
Humoral response
cell mediated response
370
What is the mechanism of humoral response to viruses
Antibody (IgA) – blocks binding
Opsonisation- coating for phagocytosis
Complement cascade prepares for removal
371
What is the mechanism of cell-mediated response against viruses
Antiviral action
Kill infected cells
Macrophages clear up
372
What is the usual time-frame for viral disease
Peaks at 7-10 days then declines
373
What is viral evasion
Interfere with specific or non-specific defence
Influenza changes coat antigen
Antigenic drift: spontaneous mutations, occur gradually giving minor changes = Epidemics
Antigenic shift: sudden emergence of new subtype different to that of preceding virus =Pandemics
374
How do bacteria enter the body
via:
Respiratory tract
Gastrointestinal tract
Genitourinary tract
Skin break
375
How is the defence mechanism affected by number of pathogens and virulence
Low number or virulence – phagocytes active
High number of virulence – immune response
376
Give 2 examples of bacterial evasion
Mycobacterium – escape from phagolysosome, live in cytoplasm
M.avium – blocks phagosome
377
What does the immune response to parasites depend on
Location in host:
Blood stage – humoral immunity
Tissue stage – cell mediated immunity
378
What are 3 types of protozoan evasion
Surface antigen variation
Intracellular phase
Outer coat sloughing
379
Why doesnt the immune system remove worms
Do not multiply in humans
Not intracellular
Few parasites carried
Poor immune response
Immune response not sufficient to kill
380
What are 2 types of worm evasion
Decreased antigen expression by adult
Glycolipid/ glycoprotein coat (host derived)
381
What is passive immunization and its 3 types
preformed antibody transferred
Transplacental transfer
Inject preformed antibody
Colostrum- milk at start of breast feeding
382
What is active immunization and its 2 types
Elicitis – protective immunity – immunological memory
Achieved by natural infection – vaccine administration
383
What are protozoa
The first animals
Single-celled eukaryotic organisms
Main biological role: consumers of bacteria, algae, microfungi
Important parasitic and symbiotic relationships
All engulf food by phagocytosis and then digest it in intracellular
384
What are the 5 major groups of protozoa
Flagellates
Amoebae
Sporozoans
Ciliates
Microsporidia
385
What are the features of flagellates
Flagellum as main locomotory organelle
Usually reproduce by binary fission
Intestinal flagellates or other body sites
386
How do amoeba move
by means of flowing cytoplasm and production of pseudopodia
387
What are the features of sporozoans
the pathogen in malaria
No locomotory extensions
All species parasitic
Most intracellular parasites
Reproduce by multiple fission
388
What are the features of ciliates
Cilia that beat rhythmically at some stage in lifecycle
2 types of nuclei – macro/micronucleus
389
What are the features of microsporidia
Production of resistant spores
Unique polar filament; coiled inside spore
390
What is malaria
Protozoan infection caused by Plasmodia sporozoan.
Transmitted by bite of female Anopheles mosquitoes
5 different species
391
What are the clinical features of malaria
Very varied
Fever almost invariable
Other common;
Chills and sweats
Headache
Myalgia
Fatigue
Nausea and vomiting
Diarrhoea
all these symptoms common to all species
392
Define antibiotics
agents produced by micro-organisms that kill or inhibit the growth of other micro-organisms in high-dilution.
393
What are 5 target sites of antimicrobials
Penicillin-binding proteins in cell wall
Cell membrane
DNA
Ribosomes
Topoisomerase IV or DNA gyrase
394
What are the 7 key groups in infection prevention and control
Infection prevention and control team
Ward teams
Microbiology/ virology laboratories
Trust management
Estates
Domestic services
Pharmacy
395
What is the most effective method of preventing cross infection
Hand hygiene
396
When to wash hands ( 5 times)
Before and after handling patients/ clients
After handling any item that is soiled
After using the toilet
Before and after an aseptic procedure
After removing protective clothing including gloves
397
When to use alcohol gel (2 times)
Following hand washing, prior to a ward based invasive procedure
Following hand washing, when caring for a patient with barrier precautions
398
What are endogenous diseases
Infection of a patient by their own flora
Important in hospitalized patients, especially those with invasive devices or surgical patients
399
What is the 90/90/90 goal for aids
90% of people living with HIV being diagnosed
90% diagnosed on ART (antiretroviral therapy)
90% viral suppression for those on ART by 2020
400
What are the 3 transmission routes for HIV
Blood
Sexual
Vertical
401
What are the 6 main benefits of knowing HIV status
Access to appropriate treatment and care
Reduction in morbidity and mortality
Reduction in mother-to-child-transmission (MTCT)
Reduction of sexual transmission
Public health
Cost-effective
402
What are the symptoms of HIV
Acute generalized rash
Glandular fever
Indicators of immune dysfunction
Unexplained weight loss or night sweats
Recurrent bacterial infections including pneumococcal pneumonia
403
What are the 9 steps of HIV replication
Attachment
Entry
Uncoating
Reverse transcription
Genome integration
Transcription of viral RNA
Splicing of mRNA and translation into proteins
Assembly of new virions
Budding
404
What are the receptors and mechanism involved in HIV infection
HIV infects cells that express CD4
Binding of gp120 to CD4 induces a conformational change in gp120
The co-receptor binding site includes a conserved bridging sheet and also amino acids in the V3 loop
405
How does HIV damage the immune system
through depletion of CD4 T-cells
406
What are the 2 markers used to monitor HIV infection
CD4 cell count
HIV viral load
407
What is the most common oppurtunist infection in HIV
PCP (pneumocystis pneumonia)
408
Who are the 7 high risk groups for HIV
Men who have sex with men
Heterosexual women
Injecting drug users
Commercial sex workers
Heterosexual men
Truck drivers
Migrant workers
