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introductory clinical sciences Flashcards

1
Q

define acute inflammation

A

the initial and often transient series of tissue reactions to injury

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2
Q

what are the stages of acute inflammation

A
  1. Initial reaction to injury
  2. Vascular - dilation of vessels and increased permeability
  3. formation of exudate - vascular leakage of protein rich fluid
  4. recruiting of neutrophil polymorph to tissue
  5. outcome
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3
Q

what are the different outcomes of acute inflammation?

A
  1. resolution
  2. suppuration - due to excess exudate
  3. organisation and repair - due to excessive necrosis
  4. progression to chronic inflammation - persistant causal agent
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4
Q

what are the clinical features of acute inflammation and why do these occur?

A
  1. Rubor/redness - due to vasodilation
  2. Calor/heat - due to hyperaemia and chemical mediators of inflammation
  3. Tumor/swelling - due to leakage of exudate (oedema) and physical mass of cells migrating
  4. Dolor/pain - due to stretching and distorting of tissues, and bradykinin, prostaglandins and serotonin.
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5
Q

What is the diagnostic histological feature of acute inflammation?

A

Accumulation of the neutrophil polymorph in extracellular space

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6
Q

What are the stages of emigration of the neutrophil polymorph to a tissue?

A
  1. margination
  2. pavementing
  3. passing through spaces between endothelial cells
  4. pass through basal lamina and migrate into adventitia
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7
Q

define chronic inflammation

A

subsequent and often prolonged tissue reactions following the initial response to tissue injury.

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8
Q

which cells are involved in chronic inflammation and what are their roles?

A
  1. Macrophages - phagocytose, carry debris away, may present antigens
  2. fibroblasts - form collagen
  3. lymphocytes - antibodies attract other cells, immunological memory
  4. endothelial cells - line capillary blood vessels, become sticky in area so inflammatory cells adhere to them, Become porous so that inflammatory cells pass into tissues. Grow into areas of damage to form new capillaries
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9
Q

what is the role of the neutrophil polymorph in acute inflammation?

A

contain granules with enzymes to kill bacteria, die at scene releasing chemicals to attract other cells

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10
Q

describe and explain the causes of inflammation

A
  1. microbial infections
    Viruses kill cells by intracellular multiplication
    Bacteria release endo and exotoxins that kill cells
  2. hypersensitivity reactions - when an altered state of immunological responsiveness causes an inappropriate or excessive immune reaction
  3. physical agents - trauma, UV, burns, frostbite
  4. chemicals
  5. tissue necrosis releases peptides which causes an inflammatory response.
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11
Q

what is a granuloma made of?

A

cluster of epitheloid histiocytes

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12
Q

explain how a histocytic giant cell is formed

A
  • when particulate matter ingestible by macrophages accumulates which have cell walls containing mycelia acids
  • foreign particles unable to be digested by just one macrophage
  • macrophages fuse when trying to engulf the same particle
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13
Q

why do blood clots not form in a normal circulation?

A
  1. laminar flow - blood flows in middle of vessel

2. endothelial cells not sticky when healthy.

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14
Q

define thrombosis

A

formation of a solid mass from blood constituents in an intact vessel in a living person

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15
Q

define embolism

A

the process of a solid mass in a blood vessel being carried through the circulation to a place where it gets stuck and blocks the vessel

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16
Q

what are the four possible outcomes of a thrombus

A
  1. lysis and degeneration
  2. bits break off
  3. organisation
  4. recanalisation - capillaries grow through thrombus
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17
Q

define infarction

A

reduction in blood flow to a tissue that is so reduced that it cannot support mere maintenance of the cells in that tissue, causing cell death

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18
Q

why does a reperfusion injury happen

A

due to reactive oxygen species being released when o2 is restored causing damage to cells

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19
Q

what are the three causes of thrombosis (and explain)

A
  1. change in vessel wall - damage exposes collagen to which platelets can stick, RBC can get trapped also. combination of RBC and platelets form a thrombus. (platelets cause fibrinogen —-> fibrin)
  2. change in blood flow - laminar —> turbulent flow in damaged vessels. Slower blood flow causes RBC to stick to endothelial wall
  3. change in blood constituents - clotting proteins
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20
Q

define apoptosis

A

programmed cell death

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21
Q

define atheroma

A

degeneration of the walls of arteries caused by accumulated fatty deposits and scar tissue

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22
Q

how does an atheroma form

A
  1. LDL’s infiltrate epithelium
  2. macrophages drawn to site
  3. they fill with lipids
  4. become foam cells
  5. accumulate in endothelial lining
  6. lesions called atheroma’s form
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23
Q

describe the positives and negatives of apoptosis

A 
good points
. kill bad cells
- during embryonic development they die in certain areas 
- dead cells in the epidermis and gut
bad points
- lack of apoptosis = cancer
- in HIV there is too much
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24
Q

how is apoptosis started by a cell

A
  • due to DNA damage (base alteration, single strand or double strand break)
  • detect via P53 protein - can switch on apoptosis if too much cell damage
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25
Q

define necrosis

A

traumatic cell death

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26
Q

define and give an example of hypertrophy

A

increase in size of a tissue by increase in size of cells - muscle growth

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27
Q

define and give an example of hyperplasia

A

Increase in size of a tissue by increase in number of cells - uterine growth during pregnancy

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28
Q

define atrophy

A

decrease in size of a tissue by either decrease in number of cells or size of cells

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29
Q

define metaplasia and give an example

A

change in differentiation of cell from one fully differentiated cell type to another - barrett’s oesophagus

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30
Q

define dysplasia

A

morphological changes seen in the progression of cells with cancer

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31
Q

define neoplasm

A

a lesion resulting from the autonomous or relatively autonomous abnormal growth of cells that persists after the initiating stimulus has been removed

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32
Q

what are the two components of a neoplasm

A
  1. neoplastic cells
    - derive from nucleated cells
    - usually monoclonal
    - have growth pattern and synthetic activity related to the parent cell
  2. stroma
    connective tissue network that provides nutrients and mechanical support to the cells
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33
Q

how does a neoplasm under 2mm get its blood supply

A

passive diffusion

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34
Q

compare the properties of benign and malignant neoplasms

A 
Benign 
- localised 
-non invasive 
- slow growth rate
- low mitotic activity
- closely resemble normal tissue
- encapsulated
- exophytic growth (up and out)
Malignant 
- non localised (metastases)
- rapid growth 
- high mitotic activity 
- variable resemblance to normal tissue
- poorly defined or irregular border
- hyper chromatic nuclei
- pleomorphic nuclei 
- endophytic growth
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35
Q

define sarcoma

A

malignant connective tissue neoplasm

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36
Q

what is the name for a benign connective tissue neoplasm of cartilage, smooth muscle, striated muscle, bone, vessels and adipose tissue

A

chondroma, leiomyoma, rhabdomyoma, osteoma, angioma, lipoma

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37
Q

define papilloma

A

benign non glandular non secretly neoplasm

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38
Q

define carcinoma

A

malignant tumour of epithelial cells

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39
Q

what is adenocarcinoma

A

malignant tumour of epithelial cells that are glandular

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40
Q

what is the name for a neoplasm of benign glandular or secretory neoplasm

A

adenoma

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41
Q

define carcinogenesis

A

transformation of normal cells to neoplastic cells through permanent genetic mutations (applies to malignant neoplasms)

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42
Q

list the types of carcinogens

A
  1. chemical
    - e.g polycyclic aromatic hydrocarbons in cigarettes
    - usually require conversion from pro carcinogens to ultimate carcinogens
  2. viral
  3. ionising and non ionising radiation
    - UVA and UVB radiation
  4. hormones, mycotoxins and parasites (biological agents)
    - hormones - oestrogen increases endometrial cancer
    - mycotoxins - alfatoxin B1 -hepatocellular cancer
    - parasites - sistosoma - bladder cancer
  5. Misc
    - asbestos
    - metals
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43
Q

list some host factors that may increase risk of cancer

A
  • race
  • diet - low fibre - carcinogens stay in GI tract longer
  • constitutional factors - age, gender
  • premalignant lesion - polyps in colon, ulcerative colitis
  • transplacental exposure
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44
Q

differentiate between carcinoma in situ, micro invasive carcinoma and invasive carcinoma

A

carcinoma in situ - non invasive group of abnormal cells
micro invasive carcinoma - partially escaped through BM
invasive carcinoma - moved to different site

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45
Q

what is the processes which a cancer moves to a different site

A

metastasis

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46
Q

what are the stages of metastasis and what factors aid this

A
  1. invasion of BM
    - collegenase
    - cathepsin D
    - urokinase - type plasminogen activator
  2. move to vessel
    - tumour cell derived motility factors
    - breakdown products of ECF
  3. intravasion
    - collagenases
  4. travel without being destroyed by immune system
    -shedding of antigens
    - aggregation to platelets
    -adhesion to other tumour cells
  5. extraversion
    -collagenases
    -adhesion receptors
  6. infiltrate new tissue
    -growth factors
  7. angiogenesis
    promoters
    -vascular endothelial GF
    - basic fibroblast GF
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47
Q

Describe the differences between innate and adaptive immunity

A 
Innate
- present from birth
- first line
- no memory
- doesnt require lymphocytes
- natural barriers
- phagocytes and natural killer cells 
- pattern recognition receptors 
- soluble mediators 
- fast acting 
- antigen non specific 
Adaptive 
-long lasting 
- slower acting 
- memory
- antigen specific 
- lymphocytes 
- antigen recognition molecules 
- secreted molecules
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48
Q

compare innate and adaptive immunity

A 
Innate 
- present from birth 
-first line response 
- phagocytic cells and natural killer cells
- no memory 
- antigen non specific 
- rapid response 
-natural barriers
- using soluble proteins and pattern recognition receptors 
Adaptive 
- antigen specific 
- slower acting
- memory 
-using lymphocytes 
- antigen recognition molecules
-secreted molecules
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49
Q

what are the three components of the innate immune system

A
  • phagocytic cells
  • soluble proteins
  • physical and chemical barriers
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50
Q

give examples of the anatomical and physiological barriers used in the innate immune system

A
  • gut acid
  • mucociliary escalator
  • low PH of vagina and sebum
  • skin as a physical barrier
  • nasal hair
  • tears - lysozyme
  • temperature/fever
  • inflammation
  • o2 tension
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51
Q

which types of soluble protein are used in innate immunity

A

Interferons
-in response to viral infection
-induce antiviral state in surrounding cells
-IFN alpha and beta produced by virus infected cells
-IFN gamma released by activated T cells
Complement
-lyse microbes directly
-increase chemotaxis (C3a and c5a)
-opsonisation (chemically modifying microbes to make more attractive to phagocytes and NK cells.) (C3b)

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52
Q

what are the cells of the innate immune system and what are their roles?

A

The polymorphonuclear leukocytes
- eosinophils
allergic reactions and parasitic infections
-basophils
parasitic infections and allergic reactions
express high affinity of IgE receptors. Binding of IgE causes degranulation releasing histamine
-neutrophils
phagocytes
contain granules - primary contain myeloperoxidase, hydrolases and defensins which combine with phagosomes containing microbes to digest them
secondary granules contain lactoferrin and lysozyme.

Macrophages

  • differentiated from monocytes
  • reside in tissues
  • phagocytosis and antigen presentation
  • remove foreign and dead microbes
  • lysosomes with peroxidase

Dendritic cells

  • APC’s
  • present Ag to T cells
  • trigger adaptive immune response

Natural Killer cells

  • kill virus infected cells and tumour cells by apoptosis
  • express CD56
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53
Q

What do pattern recognition receptors do?

A

recognise pathogen associated molecular patterns (PAMP)

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54
Q

What are the three main forms in which PRR’s are found in the body?

A
  1. secreted and circulating
  2. extracellular
  3. intracellular
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55
Q

describe the secreted and circulating PRR’s found in the body

A
  • antimicrobial peptides secreted in lining fluids from epithelia and phagocytes
  • lectins and collectins: carbohydrate containing proteins that bind carbs or lipids in microbe walls, activate complement improving phagocytosis
  • mannose binding lectin surfactant proteins A and D
  • Pentraxins can react with C protein of pneumococci, activate complement and promote phagocytosis
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56
Q

describe the extra cellular cell associated PRR’s found in the body

A

-Toll like receptors, recognise structurally conserved molecules derived from microbes
-TLR 1,2,6 gram positive lipopeptides
-TLR5 flagellin
-TLR4 viral proteins
mannose on macrophages - fungi
lectin 1 - phagocytes - betaglucans in fungal walls
scavenger on macrophages

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57
Q

describe the intracellular PRR’s found in the body

A
  • Nod like receptors detect intracellular microbial pathogens. E.g NOD 2 recognises MDP a breakdown product of peptidoglycan, activates inflammatory signalling pathways
  • RLR’s detect intracellular viral DNA - activates interferon system
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58
Q

what conditions are associated with a non functioning and hyper functioning NOD2 receptor?

A

non functioning - Chrons disease

hyper functioning - Blau syndrome - chronic granulomatous infection of eyes, skin and joints.

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59
Q

How are PRR’s linked to adaptive immunity?

A

-causes cytokine production by APC’s that can activate T cells - leading to adaptive immunity

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60
Q

what is an epitope?

A

The part of an antigen that binds to an antibody

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61
Q

what is the role of the Fc region on a antibody?

A

binds to complement, fc receptors on phagocytes, NK cells

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62
Q

what is the most common immunoglobulin class and its role?

A

IgG (70-75% of Ig)

activates complement system and causes agglutination of microbes for mass digestion

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63
Q

where is IgA found and what is its role?

A

In secretions via mucous membranes

activates complement system

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64
Q

which Ig is involved with allergic response?

A

IgE

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65
Q

On which cell is IgD found

A

immature B lymphocytes

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66
Q

What is the role of IgM

A

control of B activation and primary antibody against A and B antigens on RBC’s.

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67
Q

how does the Fab region of antibodies protect against infection?

A

allows specific binding to antigens associated with microbes

  • neutralize
  • immobilise motile microbes
  • form complexes
  • prevent binding to host cells
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68
Q

how does the Fc region of antibodies protect against infection?

A

By enhancing innate mechanisms

  • activate complement
  • bind Fc receptors (causes phagocytes to increase phagocytosis, mast cells to release inflammatory mediators, NK cells to carry out enhanced killing of infected cells)
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69
Q

describe the cells involved in adaptive immunity and their roles

A

B lymphocytes
-mononuclear leukocyte
-mature in bone marrow
-15% of blood
-express CD19+20
-recognise antigens displayed by APC’s
- differentiate into plasma cells to make antibodies
T lymphocytes
-mature in thymus
-mononuclear leukocyte
4 types:
-T helper 1 - express CD4 - help immune response to intracellular pathogens
-T helper 2 - express CD4 - help immune response to extracellular presents
-T cytotoxic killer - express CD8 -can kill cells directly
-Treg - (fox P3) dampen and regulate immune response

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70
Q

how do cells use major histocompatibility complexes to recognise antigens?

A

When a cell phagocytoses a pathogen it uses an MHC to present the pathogens antigens on its surface, this is bound to by T cells which stimulates an immune response.
In a normal healthy phagocytic cell it displays its own antigens which the T cells do not react to .

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71
Q

which chromosome are MHC genes found?

A

Chromosome 6

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72
Q

Define polymorphic

A

many alleles at a single gene locus

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73
Q

what are the two major classes of MHC and their functions?

A

Class I
-expressed by all nucleated cells
-present antigens to T killer (CD8) cells
-function is to kill cell with intracellular pathogen by inducing apoptosis
Class II
-expressed by macrophages, dendritic cells and B cells
-present antigens to CD4 T cell
- helps B cells make antibody to extracellular pathogen

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74
Q

what are the main groups of cytokine and their roles?

A
  1. interferons - viral infection
  2. interleukins - made by T cells, can be pro or anti inflammatory, cause cells to divide, differentiate and secrete factors.
  3. Colony stimulating factors - cause leukocyte production
  4. chemokines - draw leukocytes from blood into tissue or lymph organs by binding to specific receptors on cells
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75
Q

what are the stages of phagocytosis

A
  1. binding
  2. engulfment
  3. phagosome formation - acidification, cytotoxic molecules, proteolysis
  4. lysosome fusion - digestion
  5. membrane disruption
  6. secretion of h2o2, TNF, NO
  7. antigen presentation
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76
Q

write the reaction for o2 dependent killing mechanism in macrophages

A

o2- –> h2o2 —> OH. (free radical)

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77
Q

what are the stages of drug development?

A
  • lead compound identification
  • pre clinical research
  • filling for regulatory status
  • clinical trials on humans
  • marketing the drug
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78
Q

define druggability

A

the ability of the protein target to bind small molecules with high affinity

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79
Q

list as many possible ways drugs can be made (many answers)

A 
Medicines from Plants
Inorganic Elements
Organic molecules
Sulphonamide Nucleus
Bacteria/fungi/moulds
Stereoisomers
Immunotherapy Antibodies
Medicines from Animals
Recombinant proteins/steroids
DNA/transcription/gene selection
Gene Therapy 
High throughput assays/rational design
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80
Q

what does tumour necrosis factor alpha do and how can it be neutralised?

A

It is a cytotoxic factor released by activated macrophages, stimulates acute phase proteins causing endotoxin poisoning, septic shock and chronic inflammation. can be neutralised by chimeric antibody (infliximab), fusion protein (etanercept) or human antibody (adalimumab)

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81
Q

what conditions can infliximab be used for?

A

Crohn’s disease, rheumatoid arthritis, ulcerative colitis

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82
Q

what can glucocorticoids be used for and what are their adverse effects?

A

eczema, psoriasis, asthma, COPD, IBD, IA, MS, fetal lung maturation in premature birth, adrenal replacement therapy, acute iritis, reduce brain swelling.
adverse effects -
diabetes, osteoporosis, muscle wasting, peptic ulcer, cushings syndroms moon face, striae, acne

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83
Q

what is gene therapy

A

consists of a recombinant nucleic acid used in or administered to a human being with a view to regulation, repairing, replacing, adding or deleting a genetic sequence.

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84
Q

list the routes of administration of drugs

A
  • oral
  • intravenous
  • intraarterial
  • intramuscular
  • subcutaneous
  • inhalational
  • topical
  • sublingual - under tongue
  • rectal
  • intrathecal - into spinal cord
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85
Q

define passive immunity

A

the transfer of preformed antibodies or immune cells

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86
Q

compare natural and artificial passive immunity

A

natural
-the transfer of maternal antibodies across the placenta to the developing foetus, or through breast milk
-IgG of which mother had immunity
- In breast milk IgA are found
artificial
-treatment with pooled normal human IgG or immunoserum against pathogens or toxins
-used in individuals with agammaglobulinemias
-exposure to a disease that could cause complications
- when there is no time for active immunisation to give protection
-antitoxins and antivenins

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87
Q

define active immunisation

A

manipulating the immune system to generate a persistent protective response to pathogens by safely mimicking natural infection

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88
Q

what is inoculation?

A

introducing viable microorganisms into a subject

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89
Q

describe the different choices of antigen for vaccine design

A
  1. whole organism
    -live attenuated pathogen
    -e.g TB and BCG vaccine - mycobacterium bovis grown for 13 years on medium and reduced virulence
  2. whole inactive pathogen
  3. B subunit vaccines -purified molecular components as immunogenic agents
    3types:
    -inactivated exotoxins e.g diptheria toxin, tetanus toxin
    - capsular polysaccharides e.g Men C - the main antigens involved in protective immunity to encapsulated bacteria, work by blocking opsonisation
    -recombinant microbial antigens e.g bexsero
  4. synthetic peptides - aim to produce a peptide that includes immunodominant B cell epitope and can stimulate memory cell development
  5. DNA vaccine - aim to transiently express genes from pathogens in host cells leading to B and T cell memory.
    -vector injected into muscle cells and may be taken up into chromosome
  6. Recombiant vector vaccines
    -aim to imitate the effects of transient infectuon with pathogen but using a non pathogenic organism
    -introduce genes for pathogen into non pathogenic organism and introduce into host
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90
Q

what are the advantages and disadvantages of using a whole organism for vaccine design?

A

Advantages
-attenuated pathogen sets up a transient infection
-activation of full natural immune response
-prolonged contact with immune system
-memory response in T and B cells
- often only single immunisation required
- prolonged and comprehensive protection
Disadvantages
- risk of infection with disease especially in immunocompromised people
-complications
-sometimes can revert to virulent form
-can lead to serious outbreak in areas with poor sanitation

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91
Q

what are the advantages and disadvantages of using whole inactivated pathogen for vaccine design?

A

advantages
- no risk of infection
-storage less critical
-a wide range of antigenic components are present so good immune response possible
disadvantages
-tend to just activate humoral responses not cells
-without transient infection the immune response can be quite weak
-requires boosters
-patient compliance can be an issue

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92
Q

what are the advantages and disadvantages of using B subunit vaccines?

A 
advantages 
-safe 
-no risk of infection 
-easier to store and preserve 
disadvantages 
-less powerful immune response 
-repeated vaccinations and adjuvants 
-consider genetic heterogeneity of population by choice of antigen
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93
Q

what are the difficulties of using synthetic peptides in vaccines?

A
  • peptides can be stimulatory or suppressive
  • most b cell epitopes conformational
  • HLA presentation of peptides essential
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94
Q

what are the advantages and disadvantages of using DNA in vaccines?

A 
advantages 
-safe 
-no requirement for complex storage 
-drug delivery can be simple and adaptable to widespread vaccination programs 
disadvantages 
-mild response - boosters needed
-no transient infection
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95
Q

what are the advantages and disadvantages of using recombinant vector vaccines?

A 
advantages 
-ideal stimulus to immune system 
-produce memory 
-safe 
-flexible -different components can be engineered in
disadvantages 
-require refrigeration for transport
-can cause illness in immunocompromised people
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96
Q

what is an adjuvant + examples

A
  • any substance added to vaccine to stimulate immune system
  • whole killed organisms
  • aluminium slats - potentiate opsonised phagocytosis
  • TLR agonists
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97
Q

define allergy

A

abnormal response to harmless foreign material

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98
Q

define hypersensitivity

A

a set of undesirable reactions produced by the normal immune system

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99
Q

define atopy

A

the tendency to develop allergies against common environmental allergens

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100
Q

what are the stages of an allergic response

A
  1. IgE binds to its high affinity receptor FcεRI on immune cell
  2. cell becomes coated with IgE
  3. allergen binds to IgE causing clustering of IgE on surface by receptor crosslinking
  4. cellular responses
  5. release of inflammatory mediators and cytokines from mast cells and basophils
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101
Q

what is the function of FcεRII receptor

A

regulation of IgE synthesis
trigger cytokine release by monocytes
trigger antigen presentation by cells

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102
Q

which cells express FcεRI receptors?

A
  • eosinophils
  • mast cells
  • basophils
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103
Q

what is the role of a mast cell in the allergic response?

A

-main effector of IgE
-contains many preformed compounds that are released when IgE binds
contains:
-histamine - causes increased vascular permeability, vasodilation, cholinergic reflex (bronchoconstriction)
- chemotactic factors - cytokines leading to eosinophil attraction and activation
- proteases
-proteoglycans
-prostaglandin D2 - sm contraction
- platelet activating factor - increases platelet aggregration, degranulation, neutrophil secretion, increased vasc permeability

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104
Q

what can activate a mast cell?

A
  • allergens
  • bacterial/viral agents
  • phagocytosis of enterobacteria
  • cold/mechanical deformation
  • aspirin, NO, latex, proteases
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105
Q

what properties must an allergen have?

A
  • low conc
  • nasal/skin delivery
  • particulate delivery of antigens
  • presence of pathogen associated molecular patterns
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106
Q

what are the symptoms of anaphylaxis?

A

cv - vasodilation, increased permeability, decreased BP
resp - bronchial sm contraction, mucus
skin - rash, oedema
GI - sickness, pain

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107
Q

which cell influxes into lungs in an asthma attack?

A

eosinophils

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108
Q

describe the different treatment strategies for asthma

A
  1. desensitisation
    - increase doses of antigen
  2. prevent IgE production
    -cytokine antagonists, suppressive cytokines (TH2 response suppressed)
    -anti CD23 antibodies can decrease IgE levels e.g lumilixiab
  3. anti IgE therapy
    Xolair is a recombinant DNA derived humanized monoclonal antibody that selectively binds to IgE, inhibiting binding of IgE to FcεRI
  4. stop mast cell activation
    -membrane stabilisers
    -beta 2 agonists
    -channel blockers
    -signalling inhibitors
    -glucocorticoids - inhibit gene transcription
  5. inhibit mast cell products
    -histamine receptor antagonists
    -leukotriene, prostaglandin antagonists
    -tryptase inhibitors - prevent airway sm activation
    - PAR-2 antagonists
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109
Q

give examples of acquired and inherited immunodeficiency

A 
acquired = AIDS 
inherited = hypogammaglobulinaemia - all gamma globulins reduced
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110
Q

define autoimmunity

A

a disorder of the immune system in which a response is generated against components or products of its own tissues, treating them as foreign material and attacking them e.g rheumatoid arthritis

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111
Q

define pharmacodynamics

A

the biochemical and physiological effects of drugs

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112
Q

define receptor

A

a component of a cll that interacts with a specific ligand and initiates a change of biochemical events leading to the ligands observed effects

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113
Q

list the four main receptor types

A
  1. ligand gated ion channel
  2. g protein coupled receptor
  3. kinase linked receptor
  4. nuclear receptor
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114
Q

how do g protein coupled receptors work

A

ligand binds to extracellular receptor, causing conformational change that activates the g protein intracellularly, releases a secondary messenger

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115
Q

how do kinase linked receptors work

A

signal dimer binds, kinase activity stimulated, tyrosines are phosphorylated, intracellular proteins bind to phosphotyrosine docking sites

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116
Q

which part of nuclear receptors do DNA complexes bind to

A

zinc finger

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117
Q

define agonist

A

a compound that binds to a receptor and activates it

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118
Q

define antagonist

A

a compound that reduces the effect of an agonist

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119
Q

what is an EC50 of a drug?

A

concentration that gives half the maximal response

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120
Q

what is meant by a drug being more potent?

A

it has a larger response at a smaller concentration

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121
Q

what is meant by a drug being more efficacious?

A

it has a larger maximal response because it completely blocks a receptor

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122
Q

what is meant by intrinsic activity of a drug?

A

the ability of a drug receptor complex to produce a maximal functional response

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123
Q

give the formula for intrinsic activity

A

Emax of partial agonist/Emax of full agonist

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124
Q

which site do competitive antagonists binds to

A

orthosteric site (direct in the binding site)

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125
Q

what is muscarines antagonist

A

atropine

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126
Q

what is nicotines antagonist

A

aurare

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127
Q

what are the four types of histamine receptor and where are the commonly used

A

H1 - allergy
H2 - gastric acid secretion
H3 - CNS disorders
H4 - immune and inflammatory conditions

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128
Q

define affinity and efficacy

A

affinity - how well a ligand binds to a receptor

efficacy - how well ligand activates a receptor

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129
Q

what is it called when same receptor and agonist can cause different levels of response in different tissues

A

signal amplification

130
Q

what is the name for reduction in an agonist effect over time? why may this happen

A

tolerance

- continuous, repeated, high conc exposure

131
Q

what are the two types of enzyme inhibitor

A

irreversible - form a covalent bond with the enzyme
reversible - bind non covalent, producing different types of inhibition depending on whether it binds to enzyme or enzyme substrate complex

132
Q

how do statins work as enzyme inhibitors

A
  • HMG - CoA reductase inhibitors

- block rate limiting step in cholesterol pathway

133
Q

how are enzyme inhibitors used in parkinsons disease

A

parkinsons disease uses L-DOPA pathway
can use enzyme inhibitors to make more L-DOPA available for this pathway
-block DDC enzyme in periphery converting L-DOPA to dopamine allowing more L-DOPA to cross BBB
- block COMT enzyme in periphery breaking down L-DOPA

134
Q

give an example of a symporter and what it is inhibited by

A

NKCC channels in kidneys

inhibited by furosemide

135
Q

list the 4 types of ion channels, give examples and what they are inhibited by

A
  1. epithelium eg Enac which causes resorption of Na+ at collecting ducts - blocked by amiloride - used as antihypertensives
  2. voltage gated (Ca2+)
    -VDCC are found in membrane of excitable cells
    -Amlodipine is an angioselective inhibitor
    -causes vasodilation and reduced pvr, decreasing BP
    Na+
    Lidocaine blocks AP transmittion and signalling in heart, reducing arrthymia
  3. K+ channels (metabolic)
    -regulate insulin in pancreas - B islets of langerhans
    - Repaglenide, nateglenide and sulfonylureal lower blood glucose levels by blocking K+ channels - stimulating insulin secretion
    -treatment of type 2 diabetes
  4. receptor mediated (Cl-)
    - open when a ligand binds
    -e.g GABA - A receptor (post synaptic receptor opens Cl- channels - inducing hyperpolarisation
136
Q

describe the two types of ATPases and what inhibits them

A
  1. sodium pump - pumps Na out and K into cells against their concentration gradient
    - 3Na out 2k in
    - Digoxin inhibits mainly in myocardium, used for atrial fibrillation, heart failure and atrial flutter by lengthening cardiac AP
  2. Proton pump (K/H ATPase)
    - heterodimeric protein (product of two genes)
    - exchanges potassium from intestinal lumen with cytoplasmic hydronium
    - acidification of the stomach
    - blocked by proton pump inhibitors
    - omeprazole is an irreversible inhibitor
137
Q

define xenobiotic

A

compounds foreign to an organisms normal biochemistry such as any drug or poison

138
Q

define pharmacokinetics

A

the action of drugs in the body, including absorption, distribution, metabolism and elimination

139
Q

what is the rate of diffusion of a drug proportional to?

A
  • concentration gradient
  • area
  • permeability
  • inversely proportional to thickness
140
Q

define absorption of a drug

A

the process of transfer from the site of administration into the systemic circulation

141
Q

what are ABC proteins e.g P-gp

A

ATP binding cassette for active transport

P-gp removes a wide range of drugs from the cytoplasm to ECF, it is multi drug resistant (MDRI)

142
Q

are ionised drugs lipid soluble

A

no

143
Q

What is the Pka of a drug

A

the PH at which half is ionised and half unionised

144
Q

in which ways is the absorption of an oral drug effected?

A
  1. drug structure
    - needs to be lipid soluble to be absorbed from gut
    - highly polarised drugs tend to be only partially absorbed with much being passes in faeces
    - some unstable at low PH
  2. drug formulation
    - capsule or tablet must disintegrate and dissolve
    - some have enteric coating which is resistant to stomach acid
  3. rate of gastric emptying
    - determines how quickly drug reaches small intestine
    - slowed by food/drugs/trauma
    - faster past gastric surgery
  4. first pass metabolism
145
Q

describe the first pass metabolism (four metabolic barriers to drugs)

A
  1. intestinal lumen
    - contains digestive enzymes
    - proteases break down peptides
  2. intestinal wall
    - cellular enzymes
    - luminal membrane of enterocytes contains p-gp which limits absorption by transporting drug back into gut lumen
  3. liver
    - blood from gut delivered by splanchnic circulation directly to liver
    - avoid hepatic first pass metabolism by giving drug to region not drained by splanchnic e.g rectum
  4. lungs
146
Q

what type of drugs are giving transdermally

A

drugs that need slow and continued absorption e.g transdermal patches

147
Q

when are intradermal and subcutaneous drugs used

A

used for local effect (anaesthetic) or when deliberately want to limit absorption rate. Avoids barrier of stratum corner but is limited by blood flow.

148
Q

what is a depot injection

A

an injection that releases drug over days or weeks by incorporating drug into a lipophilic formulation and injecting intramuscularly

149
Q

define distribution

A

process by which the drug is transferred reversibly from the general circulation to the tissues as the blood concentration increases then returns from tissues to blood as blood concentration falls.

150
Q

how can albumin act as a depot for drugs

A

protein binding lowers free concentration of drug by binding irreversibly or reversibly, can then release bound drug when the plasma concentration drops.

151
Q

what is elimination of a drug

A

removal of a drugs activity in the body, either by excretion or metabolism

152
Q

define metabolism of a drug

A

the transformation of a drug molecule into a different molecule - necessary for lipid soluble drugs

153
Q

what are the two phases of drug metabolism

A

phase 1 - transformation of a drug into a more polar metabolite by unmaking or adding a functional group e.g oxidation by cytochrome p450
phase 2 - conjugation - formation of a covalent bond between the drug or its phase 1 metabolite and an endogenous substance

154
Q

in what form can drugs be excreted from the body

A

fluids - low molecular weight polar compounds
solids - high molecular weight compounds
gases - volatiles

155
Q

define bioavailability

A

the fraction of the administered drug that reaches the systemic circulation unaltered

156
Q

what does rate of distribution depend on for water and lipid soluble drugs

A

water - rate of passage across membranes

lipid - blood flow to tissues that accumulate drugs

157
Q

what is the formula for extent of distribution (Vd)

A

total amount of drug in body/plasma conc

158
Q

define clearance of a drug

A

the volume of blood or plasma cleared of drug per unit time

159
Q

define steady state of a drug

A

a balance between drug input and elimination. a drug with slow elimination will take a long time to reach steady state and it will accumulate high plasma concentrations before elimination rate rises to match drug infusion

160
Q

what is the neurotransmitter and receptor at the post ganglionic neurone of the sympathetic nervous system?

A

Noradrenaline acting on alpha/beta adrengeric receptors

161
Q

what is the neurotransmitter and receptor at the post ganglionic neurone of the parasympathetic nervous system?

A

Act acting on muscarinic receptors

162
Q

where are muscarinic receptors M1-M5 found

A

M1 - brain
M2 -heart
M3 glandular and smooth muscle - causes bronchoconstriction , sweating, salivary gland secretion
m4/m5 mainly CNS

163
Q

What is atropine and what is it used for

A

a muscarine antagonist that increases HR and decreases saliva production

164
Q

which muscarinic receptor would you block to cause bronchodilation

A

M3

165
Q

what is myasthenia graves and how can it be treated with cholinergic pharmacology

A

autoimmune destruction of nicotinic Ach receptors resulting in muscle weakness: give anti acetylcholinesterase to increase amount of Ach available to cause signalling

166
Q

What is the main alpha 1 receptor agonist and what does it cause

A

Noradrenaline, contracts sm (pupil, vessels)

167
Q

which receptor type being activated causes chronotrophic and inotropic effects on the heart

A

Beta 1 adrenergic

168
Q

what do Beta 3 receptors do

A

enhance lipolysis, releases bladder detrusor

169
Q

which adrenergic receptor relaxes smooth muscle and what is its main agonist

A

Beta 2 - adrenaline

170
Q

what does propranolol do

A

blocks beta 1 and 2, slows HR, reduces tremor but may cause wheeze

171
Q

name a beta 1 selective beta blocker

A

atenolol

172
Q

what is an adverse drug reactions

A

unwanted or harmful reaction following administration of a drug or combination of drugs under normal conditions of use and is suspected to be related to the drug

173
Q

what are the three effects adverse drug reactions can have

A
  1. side effects (therapeutic range)
  2. toxic effects (beyond therapeutic range)
  3. hyper susceptibility effects (below therapeutic effects)
174
Q

what are the 5 classifications of adverse drug reactions

A

Type A - augmented pharmacological - predictable, dose dependent, common
Type B - bizarre - not predictable, not dose dependent
Type C - chronic - steroids and osteoporosis
Type D - delayed - malignancies after immune suppression
Type E - end of treatment - e.g withdrawal from drugs

175
Q

what are the causes of adverse drug reactions

A
  • multifactorial
  • drug drug interactions
  • receptor abnormality
  • abnormalities in drug metabolism
  • pharmaceutical variation
  • immunological
  • abnormal biological system unmasked by drug
176
Q

describe type A adverse drug reactions

A
  • augmented pharmacological
  • extension of primary effect
  • secondary effects
177
Q

describe type B adverse reactions

A
  • not predictable, not dose dependent
  • life threatening
  • can be idiosyncrasy (unusual feature of a person/ genetic abnormality/ enzyme deficient)
  • can be allergy of hypersensitivity
178
Q

what are the four types of allergic reaction

A

Type 1 -immediate anaphylaxis (IgE) e.g penicillin allergy
Type 2 - cytotoxic antibody (IgM, IgG) e.g haemolytic anaemia
Type 3 - immune complex deposition e.g procainamide induced lupus
Type 4 - delayed hypersensitivity T cell. e,g contact dermatitis

179
Q

teratogenesis in foetus of mothers taking thalidomide for morning sickness is an example of which adverse drug reaction

A

Type D - delayed

180
Q

what are the patient and drug related risk factors for ADR’s

A
  • gender (women)
  • elderly
  • neonatal
  • polypharmacy
  • genetics
  • allergies
  • hepatic/renal impairment
  • adherence problems
  • steep dose-response curve
  • low therapeutic index (small gap between toxic and therapeutic dose)
181
Q

what is the yellow card scheme

A

used to collect suspected adverse drug reactions

182
Q

why are not all ADR’s reported

A
  • ignorance (unsure how)
  • diffidence - don’t want to look silly
  • fear - legal liability
  • letargy - too busy
  • guilt - they may have caused harm
  • ambition - i would rather collect ADR’s and publish them
  • complacency - only safe drugs marketed
183
Q

what should you report on a yellow card

A

all suspected reactions for black triangle drugs (undergoing additional monitoring) and herbal medicines
- all serious suspected reactions for established drugs, vaccines, drug interactions

184
Q

describe type 1 hypersensitivity reactions

A
  • acute anaphylaxis
  • prior exposure to antigen
  • IgE antibodies formed after exposure
  • IgE becomes attached to mast cells or leukocytes
  • reexposure causes mast cell degranulation
185
Q

describe type 2 hypersensitivity

A
  • antibody dependent cytotoxicity
  • drug or metabolite combines with a protein
  • body treats as foreign and forms antibodies (IgG, IgM)
  • antibodies combine with antigen and complement activation damages the cells
186
Q

describe type 3 hypersensitivity reactions

A
  • immune complex mediated
  • antigen and antibody form large complexes and activate complement
  • leukocytes attracted and release inflammatory mediators
187
Q

describe type 4 hypersensitivity reactions

A
  • lymphocyte mediated
  • antigen specific receptors develop on t lymphocytes
  • local or tissue allergic reaction
188
Q

list the features and management of anaphylaxis

A 
features 
- rapid onset 
- rash
- swelling
-SOB 
-hypotension 
- CA 
Management 
- ABC 
- IV fluids
-IV antihistamine 
- IV hydrocortisone 
- adrenaline
- stop drug
189
Q

how can adrenaline be used in management of anaphylaxis

A
  • vasoconstriction - inc PVR and BP and coronary perfusion via a1 adrenoreceptors
  • stimulation of beta1 adrenoreceptors - positive inotropic and chronotropic effects on heart
  • bronchodilates via beta 2 adrenoreceptors
  • decreases release of inflammatory mediators by increasing intracellular c-AMP.
190
Q

what do opioids do

A

inhibit the release of pain transmitters at spinal cord and midbrain and modulate pain perception in higher centres - euphoria - changes the emotional perception of pain

191
Q

what is meant by tolerance of a drug

A

down regulation of the receptors a drug acts on with prolonged use - need higher doses to achieve the same effect

192
Q

why may codeine and tramadol have a reduced effect in some of the population

A

the enzyme that converts them from prodrug to metabolically active form (CYP2D6) is reduced or absent

193
Q

define pathogen

A

organism that causes/ is capable of causing disease

194
Q

define commensal

A

organism which colonises the dos but causes no disease in normal circumstances

195
Q

define opportunistic pathogen

A

microbe that causes disease if host defences are compromised

196
Q

define virulence/pathogenicity

A

the degree to which a given organism is pathogenic

197
Q

define asymptotic carriage

A

when a pathogen is carried harmlessly at a tissue site where it causes no disease

198
Q

what colour does gram negative bacteria stain

A

PINK

199
Q

what colour does gram positive bacteria stain

A

Purple

200
Q

give an example of a gram negative cocci

A

Neisseria

201
Q

what does an alpha haemolytic gram positive streptococcus do to a blood agar plate and why

A

turns the agar green, because H202 interacts with the haem

202
Q

how do we classify different beta haemolytic strep

A

by antigenic group (A,B,C,G)

203
Q

what happens during a coagulase test if staphylococcus aureus is present

A

the liquid coagulates

204
Q

how do we differentiate between s.pneumoniae and other gram positive alpha haemolytic streptococci

A

using an optochin test -

205
Q

how do we differentiate between s.pneumoniae and other gram positive alpha haemolytic streptococci

A

using an optochin test - spneumoniae is sensitive

206
Q

what are the virulence factors of staph aureus

A
  • pore forming toxins - make holes in mammalian cell walls causing them to lose their contents and die e.g alpha haemolysin and PVL (haemorrhage pneumonia)
  • proteases
  • toxic shock syndrome toxin - stimulates cytokine release
  • protein A (binds Ig’s wrong way round)
207
Q

what are the conditions associated with staph aureus

A 
pyogenic
-abscesses
-wound infections
-impetigo  (sores on face)
-septicaemia 
-osteomyelitis
-pneumonia
-endocarditis
toxin mediated 
-TSS
-food poisoning
coagulase negative 
-infected implants 
-endo carditis 
-septicaemia
208
Q

give two examples of coagulase negative staphylococci, what these cause and their virulence factors

A

s. epidermis
- opportunistic infection in debilitated, catheters, prostheses
- virulence = biofilms form (community of bacteria form extracellular polysaccharide which antibiotics cannot break down)
s. saprophyticus
- acute cystitis
- haemaglutinin for adhesion
- urease - kidney stones

209
Q

what is lance field grouping

A

a method used to group catalase negative coagulase negative bacteria based on carbohydrate cell surface antigens.

210
Q

give an example of a lance field group class A bacteria

A

s. pyogenes

211
Q

what type of bacteria is s. agalactiae and where is it usually found

A

neonatal infections - it is a lance field group B beta haemolytic streptococci

212
Q

what can streptococcus pyogenes cause and what are its virulence factors

A
  • wound infections - cellulitis
    -tonsilitis and pharyngitis
    -otitis media
    -impetigo
    -scarlet fever
  • can give rise to immunologically mediated complications e.g rheumatic fever and glomerulonephritis
    virulence;
    capsule - hyaluronic acid
    M protein - surface protein that encourages complement degradation
    enzymes - streptokinase (lyses clots) hyaluronidase (spreading)
    toxins - streptolysins 0+S (binds cholesterol), erythrogenic toxin (exaggerates response)
213
Q

what does s.pneumoniae cause and what are its virulence factors

A

-normal commensal in oropharynx in 30% of population
-pneumonia
-otitis media
-sinusitis
-meningitis
virulence:
-capsule
-inflammatory wall constituents
-cytotoxin

214
Q

what are viridian’s streptococci?

A

a group of alpha haemolytic streps that aren’t sensitive to optochins test.
oral strep that can cause dental caries and abscesses

215
Q

name two gram positive rods

A

corynebacterium

listeria

216
Q

what is corynebacterium diphtheria’s main virulence factor

A

a toxin that inhibits protein synthesis by inactivating elongation factor 2 (for which the vaccine is a toxoid)
causes diphtheria

217
Q

what is the first stage of classifying gram negative bacilli

A

appearance on Macconkey or CLED or XLD - lactose fermenting or non lactose fermenting

218
Q

give examples of non lactose fermenting gram negative bacilli

A

shigella
salmonella
pseudomonas
proteus

219
Q

what test do we do to classify non lactose fermenting gram negative bacteria and what are the findings of this

A

oxidase test

  • positive = pseudomonas
  • negative = coliforms/enterobacteriaceae e.g proteus, shigella
220
Q

how is e.coli classified by a lactose fermenting test

A

lactose fermentation positive

221
Q

list the five main types of gamma proteobacteria

A
  1. enterobacteria e.g escherichia coli, salmonella and shigella
  2. vibrio cholerae
  3. pseudomonos aeruginosa
  4. haemophilus influenzae
  5. legionella pneumophila
222
Q

describe why some bacteria are “lactose fermenting” and some aren’t

A

Mac monkey agar contains bile salts, lactose and PH indicator, if a bacteria can ferment lactose it produces lactic acid and changes the PH of the agar e.g e.coli

223
Q

list 6 things e.coli can cause to its host

A
  1. wound infections
  2. UTI
  3. gastroenteritis
  4. Traveller’s diarrhoea
  5. bacteraemia
  6. meningitis
224
Q

how is shigella different to E.coli

A

contains a virulence plasmid = shiga toxin

225
Q

what are the symptoms of shigellosis and the mechanism behind which shigella causes this

A
  • severe bloody diarrhoea
    -frequent stools
  • blood and pus
    -acid tolerant - small amount of bacteria needed to become infected
    mechanism
  • entry through colonic M cells overlying payer’s patches
    -shigella enters M cell and induces apoptosis of macrophage then polymerises epithelium actin allowing to propel itself laterally through the epithelium
226
Q

which species of salmonella is responsible for salmonellosis

A

s. enterica

227
Q

what are the three forms of salmonellosis

A
  1. gastroenteritis
    - food poisoning
    - localised
  2. enteric fever - thyphoid
    - systemic disease
  3. bacteraemia
228
Q

what is the pathogenesis of gastroenteritis with salmonella

A
  1. bacterial mediated endocytosis
  2. induction of chemokine release
  3. neutrophil recruitment and migration
  4. neutrophil induced tissue injury
  5. fluid and electrolyte loss - diarrhoea
229
Q

what is the pathogenesis of enteric fever with salmonella

A
  1. bacteria mediated endocytosis
  2. transcytosis to basolateral membrane
  3. enter blood stream via thoracic duct - systemic spread
230
Q

describe vibrio cholerae, what it causes and its virulence factors

A

-facultative anaerobe
-saline environments
-from shellfish or drinking contaminated water
-causes cholera - most sever diarrhoea disease
-faecal - oral route - high I.D required (Acid sensitive)
-can lose 20/L per day + electrolytes = dehydration/death - 60% mortality
-no blood/pus/fever - not dysenteric
virulence :
-TCP pili - required for colonisation
-cholera toxin modifies ion transporter = massive H20 loss

231
Q

what does pseudomonas aeruginosa cause and what are its virulence factors

A

acute infections
-localised (burn/surgical wounds, UTI, keratitis)
-systemic (bacteraemia)
-icu patient infections
chronic
-in CF patients
virulence
-twitching motility
-multiple toxins e.g TOXA - inhibits protein synthesis, HCN (cyanide)
- in CF lung undergoes phenotypic conversion to a mucoid form which offers extra protection to the bacterium, the frustrated neutrophils then produce ROS causing lung damage

232
Q

what does haemophilus influenza cause and what are its virulence factors

A

-nasopharyngeal carriage seen in 25-85% of population
-meningitis <5yrs and pneumonia
-epiglottitis, sinusitis and otitis media
-bacteraemia
-CF and COPD infections
virulence
- pili - adherence to epithelium and mucin
- capsule - can penetrate nasopharyngeal epithelium
-LPS endotoxin - inflammation

233
Q

describe legionella pneumophila

A
  • legionnaires disease - severe pneumonia
  • immunocompromised
  • fastidious - culture on chocolate agar
  • man made aquatic environments
  • replicate within freshwater protozoa
  • can infect alveolar macrophages
234
Q

what are the two main beta proteobacteria

A
  1. bordatella pertussis

2. Neisseria

235
Q

describe bordatella pertussis

A
  • whooping cough
  • fastidious
  • highly contagious (low I.D)
  • non specific flu like symptoms followed by paroxysmal coughing
  • pertussis toxin and SI subunit ADP
236
Q

wat are the two species of Neisseria of medical importance

A

N. meningitidis

N. gonorrhoea

237
Q

what does N meningitidis cause and what are its virulence factors

A

-low level bacteraemia or septicaemia
-meningitis when enters CSF
virulence
-antiphagocytic capsule
-Type IV pili
-LPS membrane blebs - cytokine cascade

238
Q

what does N. gonorrhoea cause and what are its virulence factors

A

-urethritis
-proctitis, gingivitis, pharyngitis
-conjunctivitis in babies of infected mothers
virulence
-type IV pili
-LPS
non capsulated

239
Q

what are the 2 main epsilon proteobacteria and what do they cause

A
  1. campylobacter
    - food poisoning
    - mild to severe diarrhoea, often with blood, usually self limiting
  2. helicobacter pylori
    - gastritis and peptic ulcer disease
    - urease generates ammonia - buffers gastric acid
240
Q

describe bacteroides

A
  • obligate anaerobes (strict)
  • rodshaped bacilli
  • commensal flora
  • opportunistic - tissues injury = peritoneal cavity infections
  • antiphagocytic capsule
241
Q

what is the life cycle of chlamydia

A
  1. multiplication
  2. conversion of reticulate body to elementary body
  3. cell lysis and release of EB’s
  4. entry by EB’s
  5. conversion of EB’s to reticulate bodies
  6. prevention of phagolysosome fusion
242
Q

which species of chlamydia causes STD

A

c. trachomatous

243
Q

what are the three important genera of spirochaetes

A
  • B. burgdorferi - lymes disease
  • L interrogates - leptospirosis
  • T pallidum - syphilis
244
Q

what is the cell wall of fungi made from

A

chitin

245
Q

what is the difference between yeast and mould

A
  • yeast = small single celled organisms that divide by budding
  • moulds for multicellular hyphae and spores
  • some fungi switch between the two (dimorphic)
246
Q

how can we treat fungal disease

A
  • selective toxicity - achieve inhibitory levels of agent at the site f infection without host cell toxicity
  • polyenes bind to ergosterol in membranes causing disruption and altering activity - they have a 10x lower affinity for cholesterol in mammalian membranes - can still cause toxicity
  • allylamines - reversible inhibitor of squalene epoxidase
  • azoles
247
Q

describe mycobacteria

A
  • aerobic, non spore forming, non motile bacteria
  • slow growing (gradual onset of disease)
  • survive inside macrophages
  • high lipid content with mycelia acids in cell wall makes mostly resistant to gram stain
  • use ziehl nelson stain or AP stain
  • use Lowenstein jensen media to culture which detects production of waste material by mycobacteria
248
Q

describe M.tuberculosis

A

-breathed in through lungs
-granulomas will form around bacteria
-settled in apex as better blood and air
-necrotic tissue will form in centre of granuloma and form a cavity with waste and bacteria
-can erode into airway walls
latent TB
-no cavity
-becomes dormant until reactivation
-can spread and reactivate elsewhere

249
Q

what are the five major groups of protozoa

A
  • flagellates e.g cardia lambia
  • amoebae e.g entamoeba histolytica
  • sporozoans e.g order haemosporidia - malaria
  • ciliates
  • microsporidia
250
Q

which species is malaria caused by

A

plasmodia

251
Q

why is malaria becoming more of a problem

A
  • increased resistance of parasites to antimalarials
  • increased resistance of mosquito to insecticides
  • ecological and climate changes
  • increased travel to endemic areas
252
Q

what are the stages of a malaria life cycle

A
  1. mosquito takes a blood meal - injects sporozoites into host
  2. liver cell infected
  3. infected liver cell ruptures and goes into blood
  4. gametocytes formed
  5. mosquito takes blood meal and ingests gametocytes
  6. microgamete fertilisation
  7. ookinete —> oocyst
  8. rupture oocyte releases sporozoites
253
Q

which two malaria species have an additional hypnozoite stage in their life cycle

A

p.ovale and p.vivax

254
Q

what are the clinical features of malaria

A
  • fever, headaches, myalgia, nausea, vomiting, diarrhoea
  • anaemia
  • jaundice
  • hepatosplenomegaly
  • black urine
255
Q

what are the clinical features of p.falcifarum/why

A
  • parasite binds to receptors on endothelial cells in capillaries and venues
  • sequestration in small vessels
  • microcirculation obstructed = tissue hypoxia
  • coma
  • ARDS
  • hypoglycaemia
  • renal failure
  • shock
256
Q

what are spike projections of a virus

A

cell receptors which died which cell they infect

257
Q

what are the stages of viral replication

A
  1. attachment - viral and cell receptors
  2. cell entry - only central viral core carrying nucleic acid and some associated proteins enter host cell
  3. interaction with host cells - use cell materials for their replication
  4. replication
  5. assembly at nucleus, cytoplasm or cell membrane
  6. release - by lysis of cell (e.g rhinovirus) or exocytosis (e.g HIV)
258
Q

list some ways viruses can cause disease

A
  1. by damage to host cells
  2. by modification of host cell structure or function e.g rotaviruses (this can be physical modification or functional)
  3. damage involving over-reactivity of the host as a response to infection e.g HepB
  4. damage through cell proliferation and cell immortalisation e.g HPV
  5. evasion of both extracellular and intracellular host defences e.g by apoptosis prevention, down regulation of interferons.
259
Q

what is the pathogenesis of the rotavirus infection?

A
  1. infects epithelial cells of the small intestine (resistant to acid PH)
  2. shortening and atrophy of the villi, flattening of epithelial cells and denuding of microvilli
  3. decreases SA of small intestine, limits production of digestive enzymes such as the disaccharides
    4 patient suffers malabsorptive state in which dietary nutrients such as sugars are not absorbed by the small intestine
  4. results in hyper osmotic effect where patient has profuse diarrhoea
260
Q

what is the pathogenesis of Hep B

A
  • following acute, symptomatic HBV infection there is a massive antibody and CTL response that results in the destruction of many virally infected hepatocytes - can cause extensive liver damage
261
Q

what happens in the HBV carrier state

A
  • limited but sustained viral replication
  • natural hepatocyte regeneration
  • proliferation of the hepatocytes due to the oncogenic properties of HBV
  • liver cell destruction by CD8 cells
262
Q

what is the pathogenesis of HPV

A
  • infection of the suprabrasal layer of genital tract
  • moves to surface through natural wear and tear
  • HPV genome may become integrated into the host cell chromosome (increased chance by mutagenic agents
  • control of viral gene expression by HPV E2 protein lost and E6+7 may be expressed
  • two cell growth and suppressor proteins, Rb and P53 are prevented from operating, resulting in cervical cell carcinoma
263
Q

what are the three groups of worms

A
  • nematodes (roundworms)
  • Trematodes (flatworms)
  • cestodes (tapeworms)
264
Q

what is Loeffler’s syndrome and how is it contracted

A
  • cough, fever, wheeze, eosinophilia due to Ascaris Lumbricoides worm larval migration through the lungs from intestine
265
Q

which worm causes ground itch and what symptoms does this worms cause

A

hookworm - then hooks onto bowel wall - commonest cause of iron deficiency anaemia - eats blood
- mild pulmonary symptoms

266
Q

how is enterovirus vermicularis (pinworm) spread

A

female lays eggs on perianal skin during night

can be spread by ingestion by next host

267
Q

what do whipworms cause

A

bloody diarrhoea
rectal prolapse due to straining
anaemia
eosinophilia

268
Q

define antibiotic

A

agents produced by microorganisms that kill or inhibit the growth of other microorganisms in high dilution

269
Q

list ways that an antibiotic can work

A
  1. binding to cell wall and inhibition of cell wall synthesis e.g beta lactams
  2. interference with nucleic acid synthesis or function
  3. inhibition of DNA gyrase
  4. inhibition of ribosomal activity and protein synthesis
  5. inhibition of folate synthesis and carbon unit metabolism
270
Q

what is the difference between a bacteriostatic and a bactericidal antibiotic

A

bacteriostatic stops the bacteria growing

bactericidal kills the bacteria

271
Q

define minimum inhibitory concentration (MIC)

A

the minimum concentration to stop reproduction of a bacteria

272
Q

what is the term used to describe the minimum amount of antibiotic required to inhibit cell wall synthesis

A

Minimum bacterial concentration (MBC)

273
Q

what are the two major determinants of antibiotic effect

A
  • concentration dependent killing ( key parameter is how high the concentration is above MIC)
  • time dependent killing ( key parameter is the time that serum concentrations remain above MIC during the dosing interval)
274
Q

how do bacteria resist antimicrobials

A
  • change it’s target - changes the molecular configuration of the binding site or masks it e.g flucoxicillin is no longer able to bind PBP of staphylococci
  • destroy it - beta lactam ring of penicillins hydrolysed by bacterial enzyme - beta lactase unable to bind
  • prevent access -modify porin channel size, numbers and selectivity e.g gram negative bacteria against amninoglycosides
  • remove antimicrobial from bacteria - proteins in bacterial membranes can act as an export or efflux pump e.g s.aureus or s. pneumoniae resistant to fluroquinolones
275
Q

what are the ways in which antibiotic resistance can develop

A
  1. intrinsic resistance - all subpopulations of a species will be equally resistant
  2. acquired resistance
    a. spontaneous gene mutation
    b. horizontal gene transfer
    i. conjugation -sharing of plasmids
    ii. transduction - insertion of DNA by bacteriophages
    iii. transformation - picking up naked DNA
276
Q

describe a gram positive and gram negative resistant organism

A 
gram positive 
-MRSA - methicillin resistant staphylococcus aureus 
- resistance gene mecA 
- encodes penicillin binding protein 2a 
-confers resistance to all B lactam antimicrobials in addition to methicillin 
gram negative 
- B lactamases 
-enzymes hydrolysing penicillins 
-TEM-1 in e.coli
277
Q

in chicken pox how does the skin lesion change over time

A
  • macule
  • papule
  • vesicle
  • pustule
  • crust
278
Q

what is the brief pathogenesis of shingles

A
  1. primary infection = chicken pox
  2. virus migrates along dorsal root or cerebral ganglion sitting dormant
  3. localised reactivation - shingles
279
Q

which family and genus is HIV virus part of

A

Retroviridae family - have RNA instead of DNA which is copied into DNA by reverse transcription and incorporated into the host cell t allow gene transcription
Lentivirus genus - long incubation period viruses

280
Q

which clade of HIV predominates in the UK

A

Clade B

281
Q

which cell does HIV predominantly act on

A

CD4 T cell

282
Q

what are the stages of HIV replication

A
  1. attachment - HIV fuses to CD4 cell receptor - gp120 on HIV - CD4
  2. entry
  3. uncoating
  4. reverse transcription with reverse transcription enzyme
  5. genome integration
  6. transcription of viral RNA
  7. splicing of mRNA and transformation into proteins
  8. assembly of new virions
  9. budding
283
Q

what the stages of initial infection with HIV

A
  1. via mucosa
  2. local infection within a mucosal macrophage or dendritic cell established then spreads to other cells
  3. as these are APC’s some will migrate to local lymph node to present antigen to T cells, infecting them
  4. T cells leave lymph node and enter blood causing viraemia
  5. viral load initially comes down again as CD8 cells respond, but antigens change so often that the immune response cannot control it
284
Q

what defines a person as a “long term non progressor” of HIV

A

CD4 count > 600cells/ml in absence of treatment

-may be due to genetic factors ccr5d32 AND VIGOUROUS ctl RESPONSES

285
Q

what are the mechanisms of CD4 T cell depletion in HIV

A
  • direct cytotoxicity of infected cells
  • impaired cell homeostasis
  • bystander cell killing - apoptosis
  • decreased production and development
  • humoral immune system always on - polyclonal antibody production - unable to produce antibodies to other infections
286
Q

what are UNAIDS 90/90/90 goals for HIV

A
  • 90% living with HIV diagnosed
  • 90% of these on antiretroviral therapy (ART)
  • 90% of these viral suppression
287
Q

what number of CD4 cells must someone have to be defined as progressed to AIDS

A

less than 200

288
Q

what are the three ways HIV can be transmitted

A
  • sexual
  • blood
  • vertical - mother to child
289
Q

How can HIV be prevented

A
  • circumcision - reduced the ability of HIV to penetrate, the inner foreskin contains many langerhans cells that are very susceptible, these are removed
  • PreP - Pre exposure prophylaxis
  • PEP - post exposure prophylaxis - take antiretrovirals within 72 hours for 28 days
  • behavioural - appropriate sex ed, less changing of sexual partners
  • STI control - more likely to pass on HIV if have an ulcerative STD
  • HAART - highly active antiretroviral therapy
290
Q

what are the advantages of a HIV POCT

A
  • point of care test
  • community outreach
  • earlier diagnosis in non healthcare seeking individuals
  • increase patient choice
  • reduce transmutation
  • reduce complications
291
Q

describe the three clinical stages of HIV

A
  1. acute primary infection: acute seroconversion illness
    - transient immunosuppression + fall in CD4 count - followed by gradual rise
    - acute rise in viral load, then fall to set point
  2. asymptomatic phase
    - progressive loss of CD4 T CELLS
    - clinical latency
  3. AIDS - acquired immune deficiency syndrome
    - markers CD4 <200, HIV viral load
292
Q

what are some AIDS defining conditions

A
  • candidiasis - fungal infection
  • mycobacterium TB
  • extra pulmonary cryptococcosis
  • toxoplasmosis of internal organs
  • Non Hodgkins lymphoma
  • Primary CNA lymphoma
293
Q

what symptoms are associated which each phase of HIV

A
  1. primary infection
    - lethargy
    - weight loss
    - abrupt onset of non specific symptoms
    - depression
  2. clinically latent phase
    - persistent generalised lymphadenopathy
    - enlarged lymph nodes involving at least 2 non contiguous sites other than inguinal nodes
    - high IgG
  3. Early symptomatic HIV
    - oral/vaginal candida
    - oral hairy leukoplakia
    - listeriosis
    - cervical dysplasia
    - PID
    - peripheral neuropathy
  4. AIDS
    - pneumocystitis pneumonia
    - oesophageal candida
    - wasting
    - kaposi sarcoma
294
Q

what 3 respiratory diseases are linked with HIV

A
  1. bacterial pneumonia
  2. TB
  3. pneumocystitis pneumonia (PCP)
295
Q

what 3 CNS mass lesions are associated with HIV

A
  1. cerebral toxoplasmosis
  2. primary CNS lymphoma
  3. Tuberculoma
296
Q

which 3 types of meningitis are associated with HIV

A
  1. cryptococcal
  2. tuberculous
  3. pneumococcal
297
Q

which 3 ophthalmic lesions are associated with HIV

A
  • CMV
  • toxoplasmosis
  • choroidal tuberculosis
298
Q

which 3 neoplasms are associated with HIV

A
  • lymphoma
  • cervical neoplasm
  • kaposi’s sarcoma - vascular
299
Q

what are the 3 main HIV drug types

A
  1. reverse transcriptase inhibitors
  2. protease inhibitors - stop viral replication
  3. fusion inhibitors - stop viral attachment
300
Q

what were the public health targets for HIV management in 2015

A
  1. reduce sexual transmittion of HIV by 50% by 2015
  2. reduce transmutation of HIV in people who inject drugs by 50%
  3. eliminate new MTCT cases (vertical transmittion)
  4. reach 15 million people living with HIV with antiretroviral treatment
  5. reduce tuberculosis deaths by 50%
301
Q

which viruses cause chicken pox and shingles respectively

A

chicken pox
- varicella zoster
shingles
- herpes zoster

302
Q

what colour does pseudomonas go on an oxidase test

A

purple

303
Q

what colour does shigella go on XLD agar

A

red

304
Q

what colour do lactose fermenting bacteria go on Mac conkey agar

A

pink

305
Q

what is the treatment of non MRSA staph aureus

A

-flucloxacillin

306
Q

give examples of classes and specific antibiotics that work by inhibiting petidoglycan cell wall synthesis

A
  • Beta lactams - penicllin, cephalosporin, carbapenines

- glycopeptides: vancomycin

307
Q

give examples antibiotics that work by inhibiting nucleic acid synthesis. and how do they do this?

A
  • inhibit folate synthesis: trimethoprim, sulfoamides, co-trimoxazole
  • inhibit DNA gyrase - fluroquinones - cirprofloxicin
  • RNA polymerase - rifampicin
  • DNA strand breaks - metronidazole
308
Q

give examples of classes and specific antibiotics that work by inhibiting protein synthesis

A
  • macrolides - clarithryomycin, erthyromycin
  • tetracyclines - tetracycline, doxycyline
  • aminoglycoside - gentamicin, streptomycin
309
Q

what is the treatment if a chlostridium difficile infection

A
  1. metronidazole

2. vancomycin

310
Q

what is the treatment of falciparum malaria

A

quinine

311
Q

what is the treatment of non falciparum malaria

A

chloroquine

312
Q

what is the treatment for MRSA infection

A

vancomycin

313
Q

what is the treatment of a herpes zoster infection

A
  • aciclovir

- post herpetic neurlagia - amitryptiline

314
Q

which test can be used to differentiate steptococcus from staphylococcus and what are the results

A
  • catalase test
  • staph gas bubbles (+ve catalase test)
  • strep - no bubbles (-ve test)
315
Q

which agar is used to grow fungus

A
  • sabourds agar
316
Q

what colour swab should be used for viral and bacterial cultures

A
  • green = viral

- black = bacterial

317
Q

what are the causes of tolerance

A
  • down regulation of receptors
  • exhausation of mediators
  • altered drug metabolism
318
Q

which drug is associated with an increased risk of activation of TB

A
  • infliximab
319
Q

define economic efficiency

A

It is achieved when resources are allocated between activities in such a way as to maximize benefit

320
Q

define near miss

A

an event arises during care and has the potential to cause harm but fails to develop further, thereby avoiding harm

321
Q

define adverse event

A

care that fell below the standard expected of physicians in their community

322
Q

the null hypothesis can be rejected when

A

p < 0.05

Phase2a (10 decks)

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