Week 5 Magic Bullets
Magic Bullets LO’s
Mechanisms of antibacterial resistance
Anatomy of the lower limb muscles
Applied anatomy of muscles
Pathogenesis of bacterial infections
Infection and Host defence
Respiratory Viruses
Antibiotic and antibacterial agents
Connective Tissues
Antibiotic resistance
Consent and Informed decision making
Hypotheses of Disease causation
Measuring Disease Frequency and association
Communication Skills
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Methods of Antimicrobial Resistance
Selection of Abx Treatment:
 Clinical Indication of Abx treatment: Bacteria vs. Virus
 Pathogen identification - microbiological diagnosis
 Empirical Treatment - based on the MOST LIKELY pathogen (before lab results
are available)
 ? In vitro sensitivity/resistance of pathogen to Abx
 Site of infection
 Pharmacodynamics, pharmacokinetics, toxicity
 Host factors: compromised hepatic/renal function
 Availability and cost
 Likelihood of induced resistance
Antibiotic Mechanisms: Summary
Mechanism
Abx Group
Primary Effect
Inhibition of Cell Wall Synthesis
Penicillins
Cephalosporins
Vancomycin
Bactericidal
Bactericidal
Bactericidal
Inhibition of Protein Synthesis
Aminoglycosides
Tetracyclines
Macrolides
Chloramphenicol
Bactericidal
Bacteriostatic
Bacteriostatic
Bacteriostatic
Inhibition of Nucleic Acid Synthesis
Quionolones
Fluroquinolones
Rifampin
Bactericidal
Bactericidal
Bactericidal
Inhibition of Metabolism
Sulphonamides
Trimethoprim
Isoniazid
Bacteriostatic
Bacteriostatic
Bactericidal
Cell Membrane Disruption
Polymixin B
Bactericidal
Reasons for treatment failure:
1. Poor compliance
2. Poor absorption or penetration
3. Drug interaction
4. Microbial resistance
1. Identify, with examples, the mechanisms by which micro-organisms resist the
action of antibiotics
Forms of resistance:
 Intrinsic: predictable in genus/species - less of problem
 Acquired: unpredictable - mutliple - big problem
Acquired Resistance:
 Gene encoding resistance
o Mutations - e.g. chromosomal mutations
o Evolved in response to environment: spontaneous transfer and spread of
mutations
Spreading of Resistance:
 Plasmids - exchanged/transferred/incorporated into other cells. Plasmids do not
have to be incorporated/transformed into the chromosomal DNA in order to
confer resistance, they may do specific things on their own which make the
bacterium resistant.

Conjugation:
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'Bacteria Sex' - cell to cell contact and exchange of genetic material.
How? Conjugative plasmids code for the production of surface tubules
(?Fimbriae?) which connect two cells together: these conjugative plasmids
pass quickly from one cell to another
o Can occur in G+ or G- cells
o Main mechanism for spreading of resistance.
 Tranduction
o via bacteriophage - plasmid DNA is enclosed in virus/phage
o plasmid DNA transferred to other bacterium of the same species as the
virus 'infects' all the other cells
o (?in vivo evidence?)
 Transformation:
o Free/Naked DNA taken up from environment and incorporated into
chromosomal DNA of bacterium via crossing over mechanisms
o (?in vivo evidence?)
 Transposable elements: insertion sequences flanking genes - allows DNA
movement. Can occur in 'cassettes' of resistance genes (multiple resistance
genes). Comes from transposons
Mechanisms of Resistance:
1. Exclusion of antibiotic from target binding site
o Reduced/No entry into cell
o Often intrinsic
 e.g. Penicillin/Gram Neg. - Penicllins are inaffective against gram
neg. as G- do not have significant cell wall to synthesis
 e.g. aminoglycosides and streptococci
2. Antibiotic inactivation
o Enzymes cleave/modify drug
o Intrinsic OR acquired:
 e.g. B-Lactamases
3. Drug target alteration:
o Alteration of penicillin binding position (PBP) on penicillin antibiotics
4. Antibiotic removal
o Efflux pumps: removed Abx from cytoplasm
5. Drug Action Bypass
o Use of alternate metabolic pathways
o Important in Sulfonamides, Trimethoprim, Isoniazids (affect metabolic
pathways)
o
o
2. Give examples of mechanisms of bacterial resistance to antibiotics
Acquired Antibiotic Resistance occurs as a result of genes that encode for resistance:
see above for information on how this can occur.
Beta-Lactams Resistance:
Beta Lactams enter bacteria to inhibit cell wall synthesis
Intrinsic Resistance: cannot bind G- bacteria due to change in membrane charge
Acquired Resistance:
o Antibiotic Inactivation:
 B-Lactamase enzymes produce which inactivate the B-Lactam
ring structure
 Bata-lactamases are produced by most bacteria
 Cell bound (G-) or external (G+)
 Encoded on plasmids, transposons or chromosome
 Inducible or constitutive
 Various forms:
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






Penicillinases
TEM1 and SHV1 types
ESBL mutant types
Amp C cephalosporinases
Drug Target Alterations:
o Penicillin Binding Protein alterations (found in S. Pneumoniae)
 Prevents penicillins binding to the bacteria
o Outer Membrane Protein (OMP) changes:
 Prevents B-Lactam entry into cell
 Conferred to most G- Bacteria
Requirement to add ESBL inhibitor such as clavuronic acid (inhibits beta
lactamases)
HOWEVER: this is not useful in vivo
Glycopeptide Resistance
 Normally Glycopeptides bind to peptidoglycan precursors to inhibit cell wall
synthesis
Intrinsic Resistance: impermeability of glycopeptides across the outer membrane of Gbacteria
Acquired Resistance: Transposon mediated
 Drug Target Alteration
o Acquired Resistance: Replacement of DNA sequences from transposon
encoded sequences: proteins produced no longer bind glycopeptides
Aminoglycoside Resistance
Aminoglycosides inhibit bacterial protein synthesis initiation
Acquired Resistance:
 Drug target Alteration
o Impaired transport
o Reduced binding at ribosome target site
 Antibiotic Inactivation:
o Production of drug modifying enzymes:
 most important
 plasmid borne
 phosphorylating enzymes
 adenylating enzymes
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
acetylating enzymes
Tetracycline Resistance
Tetracyclines inhibit protein synthesis. Resistance is relatively common.
Uses: U/L RTIs, minor sepsis, GIT, skin infections, and specific pathogens e.g. Chlamydia,
Mycoplasma
Acquired Resistance:
Active Drug Efflux:
 Energy dependent pumping of drug from cell - reduces levels and ribosome
inhibition
 Mechanism:
o Plasmid borne genes
Macrolide Resistance:
Macrolides inhibit protein synthesis by binding the ribosome.
Intrinsic Resistance: low permeability Outer Membrane
Acquired Resistance:
 Plasmid borne
 Drug target alteration:
o Blocks binding of the drug by methylating adenine bases in rRNA so that
the drug cannot bind
o Gives cross resistance to all macrolides
o Especially important in S. Aureus
Quinolone Resistance:
Quinolones bind to DNA gyrase (G-) and topoisomerase IV (G+) to disrupt DNA function &
kill the cell
Acquired Resistance:
 Drug target alteration:
o Mutations in gyrases
 Active Drug Efflux:
o Decreased intracellular accumulation
Sulfonamide and Trimethoprim Resistance
Sulphonamides and trimethoprim inhibit folate synthesis which inhibits nucleotide
synthesis and inhibit metabolic pathway enzymes/substrates.
Acquired Resistance:

plasmid mediated
 Drug target alterations:
o Altered metabolic p/ways in bacterium
3. Identify and briefly describe culture techniques for pathogens and the method
of assessing antibiotic resistance in vitro.
Determining:
 minimum bactericidal concentration
 minimum inhibitory concentration
 achievable dosage in vivo (pharmokinetic studies)
 determine breakpoints: maximum achievable safe concentration in vivo vs. amount
needed to overcome bacteria
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calibrate methods to distinguish sensitivity/resistance
1. Broth Dilution:
o MIC
o MBC
o Series of broths with bacterium and differing conc. of Abx prepared
o MIC is lowest concentration that prevents growth of bacteria
o MBC is determined by agar subculture growth of broths that showed no
growths
2. Agar Diffusion:
o As for broth dilution, using agar plates
3. Disc Diffusion:
o Qualitative measure of Abx sensitivity: all give measures of the MIC
 CDS:
 Bacteria is mixed with sterile saline and washed around
agar plate
 Plate is dried (bacteria should be distributed all over the
plate)
 Series of Abx discs stamped onto the agar plate
 No growth: sensitive
 Growth: resistant
 E-test strip:
 diffusion from strip which contains a spectrum of Abx
concetrations
 MIC is taken from elliptical zone of growth intersecting
strip
 NCCLS: ?
4. Specific Resistance Testing

Muscular System & Muscles ~ Lower Limb
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BE ABLE TO IDENTIFY THE MAJOR MUSCLE IN THE LOWER LIMB
Muscles in the lower limb are grouped in 3 areas:
1. Muscles of the hip
2. Muscles of the thigh
3. Muscles of the leg
MUSCLES OF THE HIP
Muscles that attach to the hip
 Iliacus & Psoas
MUSCLES OF THE GLUTEAL REGION
Muscles of the gluteal region are grouped into superficial and deep layers
The superficial layer comprises:
 Gluteus Maximus
 Gluteus Minimus
 Gluteus Medius
The deep layer comprises:
 Piriformis
 Obturator internus
MUSCLES OF THE THIGH
Muscles of the thigh are grouped into anterior, medial and posterior muscle groups
The Anterior compartment comprises:
 Vastus muscles (vastus lateralis and vastus medialis)
Quadriceps
 Rectus femoris
femoris
 Sartorius (can be considered to be in hip or thigh)
The Medial compartment comprises:
 Adductor longus
 Adductor magnus
 Gracilis
 Obturator externus
 Tensor Facia lata
The Posterior compartment comprises:
 Biceps femoris
 Semimembranosus
 Semitendinosus
MUSCLES OF THE LEG
Muscles of the leg are grouped into anterior, lateral and posterior (superficial and
deep if you wish to be detailed!) compartments
The Anterior compartment comprises:
 Tibialis anterior
 Extensor hallucis longus
 Extensor digitorum longus
 Peroneous tertius
The Lateral compartment comprises:
 Fibularis brevis
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 Fibularis longus
The Posterior compartment comprises:
 Flexor digitorum longus
 Tibialis posterior
 Flexor hallucis longus
 Gastrocnemius
 Soleus
 Popliteus
 Tendocalcaneous
 Peroneus longus (at back of foot)
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ANTERIOR COMPARTMENT LEG MUSCLES:
 TIBIALIS ANTERIOR
 EXTENSOR DIGITORUM LONGUS
 EXTENSOR HALLUCIS LONGUS
 FIBULARIS (PERONEUS) TERTIUS
POSTERIOR COMPARTMENT LEG MUSCLES:
 GASTROCNEMIUS
 SOLEUS
 PLANTARIS
 FLEXOR HALLUCIS LONGUS
 FLEXOR DIGITORUM LONGUS
 TIBIALIS POSTERIOR
LATERAL COMPARTMENT LEG MUSCLES:
 FIBULARIS LONGUS
 FIBULARIS BREVIS
COMPREHEND THE ORGANISATION OF MUSCLE WITHIN DIFFERENT COMPARTMENTS OF THE LOWER
LIMB, THEIR NERVE SUPPLY AND ACTIONS
Gluteus Maximus
Nerve Supply
Inferior Gluteal nerve
Gluteus
Minimus/Medius
Superior Gluteal
nerve
Artery Supply*
Inferior Gluteal
artery
Superior Gluteal
artery
Piriformis
Branches of S1 and
S2
Internal pudendal
artery
Thigh – Anterior
(Thigh –
Sartorius)
Thigh – Medial
Thigh - Posterior
Femoral Nerve
Deep profundus
Obturator Nerve
Sciatic nerve
(except for the short
head of the biceps
femoris that is
supplies by the
common fibula
nerve)
Deep fibular nerve
Superficial fibular
nerve
Tibial nerve
Obturator Artery
Perforating artery
Adduction of thigh
Knee flexion
Tibial artery
Fibular artery
Extends ankle
Everts foot
Leg – Anterior
Leg – Lateral
Leg - Posterior
Action
Extends thigh
Lateral rotation
Abduct and
medially rotate
thigh
Laterally rotate
extended thigh,
abduct thigh
Knee extension
(+ hip flexion)
Posterior Tibial
Flexes ankle
artery
* I think that these artery supplies are correct, however please let me know if you find
errors with them and I will update the table
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Anatomy: Applied anatomy of the muscles. Upper/lower limb
1. Understand, demonstrate and discuss the muscles related to the shoulder, elbow,
wrist joints and the back.
Just repeating lecture notes here probably not useful. Everyone just needs to plough
through these to try to learn it. Similarly, summarising anatomy as it has been presented
is not particularly achievable or useful. There are a heap of tables etc that summarise
site, action, attachments, nerve supply etc in neat fashion in virtually every textbook.
Tried a functional/clinical approach instead. It may not mean much for exams but might
be handy for you to come back to at some stage. Haven’t listed every muscle or even
every group. Just the ones that link to certain conditions you will see time and time
again in clinical practice. This is not meant to be a complete list of issues or disorders.
Sometimes reading about a common condition can help reinforce the picture of the
anatomical structure and its function and help you remember it.
Shoulder Muscles:
Scapular stabilising muscles:
Rhomboids, trapezius, serratus anterior, pec minor (with the exception of pec
minor I think this is what the objectives mean by “back muscles”).
Function:
As a group - to control, anchor the scapula to the chest wall. The shoulder
is only attached to the skeleton via one joint, the sternoclavicular joint.
Thus, the shoulder relies heavily on the muscles securing the scapula
(shoulder blade) to the thorax, to give it a stable base upon which to
move. The scapula presents a very shallow “socket” ( the glenoid ) to the
head of humerus. This is, by design, a very mobile joint to allow us to
position our hand in all sorts of weird and wonderful positions.
Clinical Relevance:
The cost for the mobility described above is relative instability of the
“passive system” (bony configuration, ligaments, capsule). Disuse of
scapula stabilisers due to direct/ indirect injury or neuromuscular
disorders may result in wasting or disturbed patterns of recruitment of
these muscles. Rehabilitation aims to restore strength and bulk to these
muscles, but also to retrain patients in restoring normal control or
coordination of these muscles. Again - this is to provide a solid, well
controlled platform from which the shoulder can “do its thing”.
NB: Strength and control are two different things. One is about
developing the force/power abilities of the muscle – the other is about
retraining neuromuscular patterns of recruitment. Understanding these
recruitment patterns is becoming more and more relevant in terms of
understanding why injuries occur and how we can prevent them
happening in a rehabilitative sense.
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Shoulder Stabilisers
Deep Layer:
Rotator Cuff:
Anterior
:
Posterior:
Supraspinatus
Infraspinatus
Teres Minor
Function:
Subscapularis
NB: Deep muscles are best positioned to confer stability to joints. They attach
close to the centre of rotation so aren’t designed as prime movers. Along with
the ligaments, they are designed to limit (but allow) glides or translations within
the joints and approximate the surfaces throughout range as the more
shallow/superficial prime movers and their assistants produce the actual
movement available at the particular joint. You can divide most of the muscles
acting over the major articulations of the body into deep and shallow muscles to
consider their function similarly. Exceptions are probably the joints in the feet or
hands.
The cuff pretty much keeps the humeral head approximated in the centre of the
glenoid whilst the more superficial deltoid, bicep, tricep, coracobrachialis, pec
major, lat dorsi, teres major produce the movements.
Contraction of the discrete parts of the cuff will cause movement ( see “action” of
these muscles). So in part, they are thought of as assisting or helping to initiate
movement. Their main function, however, is to control movement and confer
stability to an otherwise relatively unstable joint.
Clinical Relevance
The cuff, or it’s parts, can be injured acutely in collision incidents, falls, or during
dynamic overhead activities in the home, work or sporting environment.
Dislocations or partial dislocations (subluxations) will often occur in these
incidents and underlying damage can occur to joint structures. At presentation,
pain and disability can be quite considerable.
Loss of joint integrity = relative instability = ↑demands on an already damaged
cuff, = poor cuff function = relative instability ↑ = ↑cuff demands
*A vicious cycle
You will probably see relatively more chronic injuries when it comes to the
rotator cuff. These can occur when this vicious cycle is allowed to continue after
acute, traumatic incidents. Alternatively, overuse of the cuff in any setting – but
particularly at work or in the sporting environment with overhead patterns of
use. “Overuse” is a relative term. Any significant change in loading (volume and
/or intensity) may induce changes within the cuff “quality”. These changes
usually take the form of a degeneration (rather than inflammation) of the cuff
tendons as they approach the humeral head. We will see this described as
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tendinopathy. It is now thought that compressive load upon these tendons is
what induces degenerative change – deformation of collagen and proliferation of
ground substance. Think of this as less bricks and more mortar within the
tendon tissue. The tenocytes (cells) within the tissue have a maintenance/repair
function. So the “maintenance man/person” is run off his/her feet trying to
repair damaged tissue – gets more and more ineffective and eventually “leaves
the building”
People with chronic rotator cuff dysfunction will have less pain compared to the
acute setting. They attend with nagging pain, more intense with elevation
primarily. They can limit/avoid pain by avoiding such positions. So they attend
more due to dysfunction.
Bicep
At shoulder (also acts over elbow), assists in flexion and also in adduction when
shoulder elevated ie across body (sometimes called horizontal flexion).
Clinical Relevance:
Degenerative changes to tendon of long head in later life. Picture its course in
bicipital groove where it takes a turn over top of humerus to its attachment on
glenoid. Easy to see why it might be under load ++. Also acute or chronic
injuries related to dynamic overhead activities – particularly throwing sports.
Ruptures are common in older age due to such degeneration and poor tissue
nutrient supply. Patients will present with pain (if acute) and a “popeye
deformity” in cases of rupture of this tendon. Rehab includes rehab of proximal
musculature – scapula stabilisers and cuff. Repair is rarely preformed.as the
muscle can function well (despite some loss of power) using the existing anchor
point of the short head to the coracoid process.
Elbow / Wrist:
There are rarely problems with the muscles acting over the elbow. Acute
ruptures of the distal attachment of biceps can occur in a traumatic “wrestling”
type incident or with a “catching” event with a suddenly changing or shifting
load. Degenerative changes would predispose one to such an incident.
However tendon attachments at the elbow can be problematic. Medial and
lateral elbow pain often stems from:

tendinopathy of the wrist extensors attaching at or about the lateral
epicondyle of the humerus (lateral epicondylitis – “tennis elbow”).

tendinopathy of the wrist flexors attaching at or about the medial
epicondyle of the humerus (medial epicondylitis – “golfers’ elbow”).
Rehab (in this case and with tendinopathy in general) involves manipulating
load (many variables to consider) upon these structures to firstly allow them to
recover/repair (reduce load) and then to condition them to cope with future
loading (increase load in progressive step-wise fashion).
Hand / Fingers:
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Muscular function at the wrist and hand is very detailed and complex. Ligament
and bony injuries are quite common in relative terms. In terms of musculo –
tendinous function, injuries to the finger joints are probably the most significant.
Damage to these joints can cause specific loss of function and often deformities
due to a resting imbalance of forces across joints – see “mallet finger”,
“boutonniere (button hole) deformity” and “swan neck deformity” as examples.
“Carpal Tunnel Syndrome” can cause widespread muscular dysfunction (thenar
muscles - - opponens pollicis, abductor pollicis brevis, flexor pollicus brevis, and
the lateral lumbricals due to compression of the median nerve as it passes
through a narrow channel in the wrist. The median nerve shares this channel
with several tendons. Changes in bony, tendon, or neural tissue can cause
degenerative and or inflammatory changes within this confined space and thus
compressive neuropathy.
2. Understand, demonstrate and discuss the muscles related to the hip, knee and
ankle joints.
Hip:
The hip is a relatively stable joint in terms of bony configuration, ligaments and
capsular attachments. Tears and muscle strains about the gluteal area are
uncommon. Like the shoulder, the tendons of the muscular network about the
hip are subject to tendinopathy as they approach their distal attachments after
crossing the joint. Treatment for lateral and posterior hip pain has often focused
on bursitis about the greater trochanter, ischeal tuberosity and deep to gluteus
medius. It is now thought this issue of tendinopathy plays a more significant role
than previously thought.
Control of movement at the hip has implications for function and loading not
only at the hip joint itself, but also for the structures proximal (sacroiliac joints,
lower spinal joints and tissues) and distal (knees ,ankles and associated
musculature) to the hip. Lectures have emphasised the stabilising role of the ilio
tibial tract and its muscular attachments, gluteus maximus and tensor fascia lata.
Along with other deep (stabilising) muscles in the hip, strength and control work
is often employed when treating people with low back pain for example and also
knee pain. If hip control is poor, repetitive movement patterns in a sporting or
occupational sense will cause excessive load on these distal and proximal
structures (not to mention the hip itself).
Knee:
When we consider the forces operating about the knee (tibio-femoral and patellofemoral joints), the way in which the muscular system controls movement and loading
here really is quite extraordinary. Pain about the patello-femoral joint is one of the
more common knee presentations, particularly in active, growing adolescents. Consider
all the muscles crossing the knee and how they contribute to stress upon the patellafemoral joint. Simplify this to just the medial and lateral forces acting upon the patella
as it tracks up and down upon the femur as the knee flexes and extends during walking,
running, squatting, jumping etc.
The iliotibial tract and hence gluteus maximus and tensor facia lata will tend to hold the
patella laterally. The vastus medialis and vastus lateralis will exert forces upon the
patella as their name suggests. The hamstring and adductor muscles will have an impact
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on the angulation of the knee relative to the hip and foot and thus the relative alignment
of the patella with respect to the femur.
Acute injuries or chronic conditions about the knee can change the way in which these
muscles function where they might become weak or tight for example. The coordinated
actions of the muscles as a group in terms of timing and speed of contraction will have
consequences for patella-femoral function and stress upon its weight bearing surfaces.
Thinking about the attachments and actions of the muscles, and trying to picture what
happens to the joints that they relate to can be useful. Going beyond that and reading
about injuries or conditions that you, your friends or family experience will help cement
the anatomy involved with those injuries in your memory.
When you get some spare time!
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PATHOGENESIS OF BACTERIAL INFECTIONS
1. Identify the key differences between prokaryotic and eukaryotic organisms
Eukaryotes
Algae, protozoa, fungi, plants and animals
>5μm
Diploid genome, nuclear membrane
Ribosome 80S (60S + 40S)
Cytoplasmic organelles: mitochondria, golgi body, ER
Cytoplasmic membrane: sterols
Cell wall absent/chitin
Sexual/asexual reproduction
Respiration via mitochondria
Prokaryotes
Bacteria
<5μm
Haploid, circular double-stranded DNA
Ribosome 70S (50S + 30S)
NA
Cytoplasmic membrane: no sterols
Cell wall: peptidoglycan, proteins & lipids (complex)
Asexual reproduction (binary fission)
Respiration at cytoplasmic membrane
2. List different categories of infectious agents and outline their differences.
Viruses: Obligate intracellular parasites that lack compliment enzymes necessary for
their replication and therefore rely on their host cells’ metabolic machinery for
replication. Viruses consist of a nucleic acid genome surrounded by a protein coat
(capsid) that is sometimes encased in a lipid membrane. Viruses may contain a nucleic
acid genome of DNA or RNA, but not both. For human purposes they are divided into
two main groups, the RNA viruses and the DNA viruses.
Bacteria: Bacteria are prokaryotes, meaning they have a cell membrane but lack
membrane-bound nuclei and other membrane-enclosed organelles. Most bacteria are
bound by a peptidoglycan cell wall (a polymer of long sugar chains linked by peptide
bridges). There are two forms of cell wall structures, a thick wall that retains crystalviolet stain (gram-positive bacteria) or a think wall sandwiched between two
phospholipid bilayer membranes (gram-negative bacteria). Bacteria are classified by
their gram stain (positive or negative), shape (spherical ones and cocci; rod-shaped ones
and bacilli) and need for oxygen (aerobic or anaerobic). Many bacteria have flagella that
enable movement and some possess pili, another kind of surface projection that can
attach bacteria to hots cells. Most bacteria synthesize their own DNA, RNA and proteins,
but they depend on their host for favourable growth conditions.
Other infectious agents include prions, fungi, protozoa and helminths. The table below
gives examples.
Taxonomic
Size
Site of propagation
Examples
Disease
Prions
30-50kD
Intracellular
Prion protein
Creutzfeld-Jacob disease
Viruses
20-300nm
Obligate intracellular
Poliovirus
Poliomyelitis
Bacteria
0.2-15 μm
Fungi
2-200 μm
Protozoa
1-50μm
Helminths
3mm-10m
Obligate intracellular
Extracellular
Facultative intracellular
Extracellular
Facultative intracellular
Extracellular
Facultative intracellular
Obligate intracellular
Extracellular
Chlamydia trachomatis
Streptococcus pneumonia
Mycobacterium tuberculosis
Candida albicans
Histoplasma capsulatum
Trypanosoma gambiense
Trypansoma cruzi
Leishmania donovani
Wucherria bancrofti
Trachoma, urethritis
Pneumonia
Tuberculosis
Thrush
Histoplasmosis
Sleeping sickness
Chagas disease
Kala-azar
Filariasis
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Intracellular
Trichinella spiralis
Trichinosis
3. Describe the structure and characteristics of bacteria.
Nuceloid: site of double stranded circular DNA. In the cell it is condensed and looped
into a coiled state. Essentially haploid organisms with only one allele of each gene per
cell. Nucleoid lies within the cytoplasm.
Ribosomes: Slightly smaller than those of eukaryote cells. Ribosomes are microscopic
‘factories’ found in all cells including bacteria. They are responsible for protein
synthesis. Bacterial ribosomes are never bound to other organelles as they sometimes
are (bound to the ER) in eukaryotes, but are freestanding structures distributed
throughout the cytoplasm. The differences between bacterial ribosomes and eukaryotic
ribosomes mean that some antibiotics will inhibit the functioning of bacterial
ribosomes, but not a eukaryote's, thus killing bacteria but not the eukaryotic organism
they are effecting.
Cell wall: Supports the weak cytoplasmic membrane against the high osmotic pressures
(survival). The chemical composition differs considerably between the different bacteria
species but the main component is peptidoglycan. The thickness of this peptidoglycan
layer is what is used to distinguish between the thick gram positive (20-80nm) and the
thinner gram negative cell walls (5-10nm).
Cell membrane: is a phospholipid bilayer allowing selective permeability. A key feature
differentiating prokaryotic cytoplasmic membranes to eukaryotic cell membranes is
their multifunctional nature. Protein secretion, packaging and processing, electron
transport and oxidative phosphorylation, all must be performed by the cytoplasmic
membranes in prokaryotes (unlike eukaryotic cells). The membrane is therefore
extremely protein rich allowing very little space for phospholipids.
Capsule: some species of bacteria have a third protective covering. This capsule is made
up of polysaccharides (complex carbohydrates). The capsule keeps the bacteria from
drying out and protects from phagocytosis. The capsule is a major virulence factor in the
major disease-causing bacteria, such as E. coli and s. pneumoniae. Non-encapsulated
mutants of these organisms are avirulent, i.e. they don't cause disease.
Slime layers: Like the capsule, the slime layer protects the bacteria from environmental
damages such as antibiotics. The slime layer also allows bacteria adherence.
Periplasmic space: Site of nutrient processing. This is a very active region, between
plasma and cell wall and is only present in gram-negative bacteria.
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Inclusion bodies: Are nuclear or cytoplasmic aggregates of sustainable substances,
usually proteins.
Vacuole: gas vacuoles allow for buoyancy in aquatic environments.
Flagella: Motile bacteria possess filamentous appendages known as flagella, allowing
locomotion. They are 2-3 times the length of the bacterial cell. The flagella rotates and
pulls bacteria forward.
Pili (fimbriae): Filamentous appendages much more numerous than flagella and much
shorter in length. They are important in securing adhesion between the bacteria and
host cell, although they are not the only way bacteria adhere to host cells. Involved in
bacterial mating and DNA transfer.
Endospores: survival in hostile environment; very resilient, can exist in dormant state
for long periods and germinate later.
CHARACTERISTICS
a) Metabolism
Growth phases: lag phase, exponential growth phase, stationary phase (nutrient deficit),
death phase.
Reproduction (binary Fission): uncoiling of DNA, replication of DNA, cell elongation,
septum formation and separation. Results in two daughter cells, identical to each other
and parent cell.
b) Temperature and Growth
Hyperthermophiles: 65-105°
Thermophiles: 40-80°
Mesophiles: 15-45° (grow at body temperature, almost all human pathogens)
Psychrotrophs: 2-35° (food microorganisms that can survive in fridge- food spoilage)
Psychrophiles: 5-18°
c) Sources of carbon, energy and hydrogen/electrons
Carbon sources

Autotrophs: CO2 sole or principle C source.

Heterotrophs: reduced, preformed organics (sugars, amino acids).
Energy Sources

Phototrophs: light

Chemotrophs: oxidation of organic/inorganic compounds
Hydrogen or Electron Sources

Lithotrophs: reduced inorganic molecules

Organotrophs: organic molecules
d) Antigens:
Initial division on basis of haemolysis on blood agar.
 α-haemolysis: 1-3mm greenish zone of incomplete haemolysis.
 β-haemolysis: zone of clearing/complete lysis without a market colour change.
 γ: no haemolysis.
e) Genetic characteristics:
 Ribosomal RNA: 16S (most eukaryote size is 18S) found in all bacteria.
 Genes: some common to all bacteria, others pathogen specific.
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


Molecular diagnostics permits detection and identification without culture
(quicker, can be used even if pathogen can’t be grown, can use very small
amounts).
Information encoded in: chromosomes, plasmids and transpoons.
-Constitutive genes: expressed all the time
-Inducible genes: expressed when needed.
Regulation of gene expression ensures adaptation to environment and avoidance
of
overproduction/waste.
Genetic diversity achieved by: mutation, recombination, gene transfer/exchange
(important in virulence (degree of pathogenicity) and antimicrobial resistance).
Mutations:
Spontaneous or external physical chemical factors. Involve point
mutations (single nucleotide change), deletions or insertions.
Consequences may be lethal, phenotypic change, no change, selective
advantage, repair, spontaneous loss over Subsequent replication
cycles.
Recombination:
Process by which new genetic material is inserted into the genome
via conjugation (direct
cell to cell contact mediated by fertility plasmids), transformation
(naked DNA from environment) or transduction (from a
bacteriophage).
Plasmids:
Small circular DNA molecules that are not part of the bacterium’s
chromosome. They have their own replication origins.
Transpoons:
Segments of DNA that can move about chromosome within single
organism or between different organisms. Differ from plasmids in
that they are unable to reproduce independently.
4. Identify, and discuss the functions of, the structural components of bacteria
which are involved in the pathogenesis of infection.
Adhesions: specialized structures on the cell surface of bacterium that bind to
complementary receptor sites on host cell surfaces. Allow adherence with high
specificity for certain tissues. Two types of adhesion: cell recognition by the bacterial
fimbriae and non-fimbrial adhesions regulated primarily by a large range of surface
proteins.
Capsule: well organised polysaccharide layer outside cell wall. Many bacterial
pathogens require a capsule to avoid phagocytosis and production of an extracellular
capsule is the most common mechanism by which this is achieved. Resist phagocytosis
by reducing interactions with complement and specific antibodies.
Glycocalyx: network of polysaccharides extending from bacterial surface, aids in
attachment to tissue.
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S-layer: structured protein/glycoprotein layer. Protects against ion and pH fluctuations,
osmotic stress and enzymes. Helps maintain shape and rigidity and may promote cell
adhesion to tissues.
Once inside cell, bacteria are lysed and the bacteria are released into the cell cytoplasm,
multiplying rapidly with inhibition of the host cell protein synthesis.
5. Describe the various mechanisms by which bacteria and viruses cause disease.
Whether it is viral or bacterial, for a disease process to be harmful to humans some form
of interaction between the infecting agent and the cell must occur.
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BACTERIA
1. Bacteria maintain a reservoir (before and
after infection).
2. Transport of pathogen to host: direct
contact (coughing, sneezing, body
contact); indirect contact (via soil, water
and food).
3. Attachment and colonisation by
pathogen- establishment of site of
reproduction. Depends on ability to
compete with host for nutrition.
4. Invasion of pathogen: entry into host
cells and tissue
-Production of lytic substances,
alter host tissue by attacking
ground substance, basement
membranes, degrading
carbohydrate-protein complexes
between cells or on cell surface;
disrupting cell surface.
-Passive entry: breaks, lesions in
mucous membranes, wounds,
burns.
-Once under mucous membrane,
pathogen can penetrate deeper
tissues and spread.
5. Growth and multiplication: must
find appropriate environment
(pH, temp, nutrients) will
depend on body site.
6. Leaving the host: most employ
passive mechanisms of escape
(faeces, urine, saliva).
VIRUSES
1. Entry: via body surfaces (skin,
respiratory, GIS, urogenital, conjunctiva)
Other (needle stick, blood transfusion,
insect vector).
2. Replication: at site of entry or spread
then replicate.
3. Viral spread: commonly bloodstream and
lymphatics. Sometimes via nerves.
4. Tropisms: specificities for cell, tissue or
organ.
5. Cell injury and clinical illness:
-Destruction of virus: infected cells in
target tissue and alterations in host
physiology are responsible for disease.
-Lytic infections: virus multiplies and
kills host cells immediately; new virions
released.
-Persistent infections; virus lives in host
cells and releases virions over a long
period with little damage to host cell.
-Latent infections: virus resides in cell
but produces no virions; activated later
and lytic infection occurs.
-Virus transforms cell into a cancer cell
(eg HPV).
6. Host immune response.
7. Recovery- host will either succumb to
virus or recover.
8. Virus shedding- shedding of virus back
into environment; stage where host is
infectious and can spread the virus.
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Infection and host defense
1. Identify the function of epithelial barriers and the innate non-specific defences
in the prevention of infection
Infection Control:
External Defenses:
 Epithelium
o Skin + Mucous Membranes
o Physical, chemical and biological barrier to the entry of microorganisms
o E.g. skin - shedding of corneal layer of epidermis with abrasion to rid
microorganisms from the skin
 Secretions:
o Mucous secretions: contact barrier, block CHO ligand receptor
interactions
o Sebaceous secretions: antibacterial, antifungal
o Defensins: antibacterial peptides produced in GIT - control colonisation
o Tears: antibacterial - contain lysozome
o Stomach acid - lethal to most bacteria
o Commensal organisms - compete against each other thus act as their
own biological control mechanism
 Peristaltic movement (stagnate area encourages growth)
 Mucociliary escalator (removes bacteria captured in mucous)
 Vomiting and Diarhorrea - reduces adhesion to mucous membranes
 Urine flow
 Coughing
Internal defenses: 'Innate Immunity'
CELLULAR COMPONENTS OF INNATE IMMUNITY

Phagocytic cells:
o Phagocytosis: eating
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o
o
o
o
Produce antimicrobial reaction oxygen species
Secrete inflammatory mediators
Antigen presenting cells (to T cells)
Types
 Monocyte/Macrophage:eaters
 Dendritic Cells: antigen presenters
 Neutrophils: NOT antigen presenters, eaters + killers
 ?Eosinophils?
What happens inside the Phagocyte after Phagocytosis? How does cell killing result?
Phagolysozome: membrane-enclosed organelle inside the phagocyte - where digestion of
phagocytosed material occurs
Oxygen independent killing
Effector Molecule
Function
Cationic proteins (cathepsin)
Damage to microbial membranes
Lysozome
Hydrolyses mucopeptides in the cell wall
Lactoferrin
Deprives pathogens of iron
Hydrolytic enzymes (proteases)
Digests killed organism
Oxygen dependent killing: all methods of oxidising phagocytosed pathogen. Oxidised
pathogen = dead pathogen
 Phagosome-oxidase fusion
 Generation of H2O2
 Myeloperoxidase activity
 Peroxynitrite production
 Natural Killer Cells:
o Phagocytes release interferons (cytokines) to activate the NK cells
o NK cells cause programmed cell death in affected self-cells
 React to stress molecules from affected cells
 React to non self cells or tumour cells (do not produce normal
self recognition molecules)
o Recognises and responds to antibodies
 Eosinophils:
o Anti-parasitic
o Protection of mucousal surfaces: Involved in allergy
 Basophils:
o ?Antigen presenting cell?
o Protection of mucousal surfaces: involved in allergy
 Mast cells:
o Protection of mucousal surfaces: involved in allergy
HUMORAL COMPONENTS OF INNATE IMMUNITY
 Complement system:
o Circulating proteins secreted by the liver, macrophages/monocytes OR
epithelial cells which become 'activated' under specific circumstances
o Activation:
 Mediated by Antibodies (Classical Pathway)
 Mediated by Antigens/Pathogen surface (Alternative Pathway)
 Mediated by Mannose-binding lectin (MB-Lectin pathway):
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Mannose is a sugar found on the membrane of the
invader
 Lectin binds to it
 Activation
o Activated complement proteins cleave off specific parts of themselves
and these parts aid in the killing of pathogens:
 Act as chemokines to recruit more inflammatory cells
 Opsonise pathogens (stick to them to enhance phagocytosis)
 Kill pathogens
Antimicrobial proteins
o Released by innate immune cells: causes swelling and lysis of cell
Inflammatory proteins:
o Instigates innate immune response to pathogen invasion
o e.g. IL-1, TNF-α, IL-8, histamine, bradykinin (pain), etc
Antimicrobial reactive oxygen species
o Oxidises bacteria




2. Describe the inflammatory response to infection
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1.Upon contact with pathogen - 'non self proteins' - the epithelial cells are activated (due
to damage, etc: PAIN)
2. Activated >>> cytokine and chemokine release
 E.g. Interleukins, Leukotrienes, Bradykinin, Prostaglandins, Histamine, Tumour
Necrosis Factor Alpha (TNF-α), etc, etc
 Cytokines and chemokines have paracrine (short distance cell-cell) and
autocrine (self) signalling effects on surrounding tissues
 Can be produced by any cells
 Highly pleiotrophic effects (many biological activities)
 Central to inflammatory response
3. Histamine, IL-1 and TNFα modulate changes to the endothelial cells (blood vessel
walls)
 Increased permeability (swelling)
 Increased capillary diameter (redness + heat)
 Increased adhesive properties
 Changes result in increased cell traffic and diffusion of fluid and cells through the
capillary wall

4. Phagocytic Neutrophils respond to chemokine IL-8: Cell Migration
 Cytokine activated endothelial cells express adhesion molecules: selectins
 Selectins recognise glycocalyx (sugar/CHO coating of cell membrane - specific to
each cell for 'recognition' purposes) of the innate immune cells and then tether
and roll them onto the affected endothelial cells
 Phagocytic Neutrophil is then ACTIVATED
 Epithelial cytokines activate ICAM (Intracellular Adhesion Molecule)
expression
 Selectin is shed to become an Integrin
 Cell activation changes integrin to high affinity ICAM
5. Cell migration and diapedesis:
 Neutrophil adheres and flattens to migrate between the endothelial cells
 Follows chemokine gradient towards site of infection
 Migrate readily to IL-8 made by epithelial cells that have encountered pathogens
6. Action of the Innate immune cells :
 recognise patterns and communicate with adaptive immune system
o DAMPs (damage associated molecular patterns)
o PAMPs (pathogen associated molecule patterns)
 involved in cell killing:
o phagocytosis:
 Non-Opsonic: cell recognition of PAMPs
 Opsonic: recognition of pathogens via antibodies
o reactive O2 species
o antimicrobial peptides
Picture: Tethering and Rolling
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3. Describe the cells and their functions involved in phagocytosis of invading
micro-organisms
Neutrophils:
 Phagocytosis
 Antimicrobial reactive oxygen species
 Antimicrobial peptides
 Short life span
 Rapidly produced in response to infection
 Involved in very initial, acute stages
Monocytes/Macrophages: PRIMARY signallers and eaters!
 Monocyte = immature macrophage
 Migrate into tissue >>>> become macrophage
 Different names in different areas of body
 Functions in immunity:
o Phagocytosis
o Antimicrobial reactive oxygen species
o Secrete inflammatory mediators
o Antigen presenting cells
Dendritic Cells:
 PRIMARY Antigen presenting cells
 Phagocytosis
 Secrete cytokines
4. Describe the role of: antimicrobial peptides, reactive oxygen species and the
complement system
Information as covered above:
 Antimicrobial proteins
o Released by innate immune cells: causes swelling and lysis of cell
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

Antimicrobial reactive oxygen species
o Oxidises bacteria
Complement system:
o Circulating proteins secreted by the liver, macrophages/monocytes OR
epithelial cells which become 'activated' under specific circumstances
o Activation:
 Mediated by Antibodies (Classical Pathway)
 Mediated by Antigens/Pathogen surface (Alternative Pathway)
 Mediated by Mannose-binding lectin (MB-Lectin pathway):
 Mannose is a sugar found on the membrane of the
invader
 Lectin binds to it
 Activation
o Activated complement proteins cleave off specific parts of themselves
and these parts aid in the killing of pathogens:
 Act as chemokines to recruit more inflammatory cells
 Opsonise pathogens (stick to them to enhance phagocytosis)
 Kill pathogens
5. Identify the cytotoxic action of NK cells against infected target cells:
As above:
Natural Killer Cells:
 Phagocytes release interferons (cytokines) to activate the NK cells
 NK cells cause programmed cell death in affected self-cells
o React to stress molecules from affected cells
o React to non self cells or tumour cells (do not produce normal self
recognition molecules)
 Recognises and responds to antibodies
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RESPIRATORY VIRUSES
1. Outline the major groups of viruses infecting the respiratory system, including
influenza, paramyxoviruses, rhinoviruses, coronaviruses and adenoviruses.
Viruses are obligate intracellular parasites. The most fundamental characteristic of a
virus is that it is absolutely dependent on a living host (cell) for its reproduction.
Virus Family
VIRUS
Orthomyxovirus
Paramyxoviridae
Picornaviruses
Coronaviridae
Adenoviridae
Influenza A, B, C
(RNA virus)
Respiratory syncytial
virus
(RNA virus)
Rhinovirus
(most common cause
of the common cold)
(RNA virus)
Coronaviruses
(cause 15%
common colds)
(RNA virus)
Adenoviruses
(DNA virus)
Airborne particles
(small) eg sneezing.
Widely spread by
school children
Inhalation of large
aerosol droplets
Inhalation of
droplets, contact
with contaminated
hands
Inhalation of
droplets, contact
with contaminated
hands
Transmission by
aerosol, close
contact, faecal-oral
route, or fingers
and
ophthalmologic
instruments (eye
infections)
Adults, children,
elderly, immunecompromised, elderly
with cardiac and
respiratory problems at
risk
Ubiquitous: global
pandemics, local
epidemics. More
common in winter
Infants, children (most
common cause of RT
infection in children),
adults
All ages
All ages coming into
contact with animal
carriers
Children, day care
centres, military
camps, swimming
clubs.
Ubiquitous
Incidence seasonal
Disease more
common in early
autumn, late spring
Disease more
common in winter,
early spring
Ubiquitous, no
seasonal incidence
VACCINES
Influenza A + B vaccine
(annually)
Antiviral drugs (eg
amantadine)
No vaccines.
Antiviral drugs
No vaccines.
Antiviral drugs for
infants
No vaccines
Live, attenuated
vaccine.
LOCATION
AFFECTED
URT, LRT (others
outside RT)
Respiratory tract, most
commonly LRT
Mostly limited to
URT, replicate in the
nasopharynx
URT
URT, LRT (also
affect eye, GIT)
CLINICAL
SIGNS
Sore throat, cough,
nasal congestion.
Systemic: muscle aches,
fever, chills, malaise,
Most commonly in
children: Bronchiolitis,
pneumonia
Adults: generally
common cold symptoms.
Common cold, major
factor in asthma
exacerbations.
Common cold
(afebrile), SARS.
Infants: associated
with gastroenteritis
Febrile. Bronchitis,
common cold, sore
throat,
conjunctivitis,
diarrhoea,
pneumonia
TRANSMISSION
RISK
FACTORS
DISTRIBUTION
OF VIRUS
2. Identify the steps in the viral infection cycle with particular reference to
infection of the respiratory epithelium.
Respiratory Tract as site of entry
The respiratory tract in the most common route of entry for viruses. Other common
sites of entry include mucosal linings of the alimentary, and urogenital tract, the outer
surface of the eye and the skin. The cell imposes multiple barriers to virus entry. Viruses
must overcome the mechanical barrier of the mucosal lining. This mucosal lining traps
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microorganisms where they may be carrier to the back of the throat via cilia and either
coughed or swallowed (digested and degraded).
However, viruses exploit fundamental cellular processes to gain entry to cells and
deliver their genetic cargo. Virus entry pathways are largely defined by the interactions
between virus particles and their receptors at the cell surface. These interactions
determine the mechanisms of virus attachment, uptake, intracellular trafficking, and,
ultimately, penetration to the cytosol.
Micro-organisms can avoid this by:
 Adhesions: specialised molecules, which enable binding to the receptor cell.
 Inhibiting the action of cilia.
The Human Respiratory Tract
Mucus layer
Brush border
Most transmission via the respiratory tract occurs through sneezing and coughing which
allows movement of mucosal secretions. Increased nasal secretions that accompany
many respiratory infections assist by increasing the number of virus carrying droplets
available to transmit the micro-organism.
1. Attatchment: The virus binds to the surface of the cell through adhesions.
2. Penetration: Fusion of the viral and host membranes, or uptake via a phagosome,
results in the virus carried across the plasma membrane and into the cytoplasm.
3. Uncoating: The viral envelope and/or capsid are shed and the viral nucleic acids
released. At this point the virus is no longer infective. Not until the virus has replicated
and exits cell.
5. Transcription and/or translation.
4. Virus replicates: Viruses contain either DNA or RNA (never both). Viruses
containing DNA, mRNA can form using the host’s RNA polymerase. Viruses with only
RNA must use their own RNA polymerases.
6. Assembly: Combining the replicated nucleic acid with newly synthesized
capsomeres.
7. Release: Exit from the host cell.
The epithelium may be left compromised. For example in a rhinovirus the DNA is
replicated within the cytoplasm and exists via cell lysing instead of budding. This results
in epithelial damage, and thus prone to secondary infection. This was seen in Mrs A’s
case in Magic Bullets.
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3. Identify the location in the respiratory system typically infected by these
agents, and the clinical pattern invoked.
Upper Respiratory Infections: Common Cold, Sinusitis, Pharyngitis, Epiglottitis and
Laryngotracheitis.
Most upper respiratory infections are of viral aetiology.
Common Cold
Aetiology: Common colds are the most prevalent entity of all respiratory infections.
Rhinoviruses are the most common pathogens. Coronaviruses, Parainfluenza viruses,
respiratory syncytial virus, adenoviruses and influenza viruses have all been linked to
the common cold.
Pathogenesis: direct invasion of epithelial cells of the respiratory mucosa, but
destruction and sloughing of these cells or loss of ciliary activity depends on the specific
organism involved. There is an increase in both leukocyte infiltration and nasal
secretions.
Clinical Manifestations: After an incubation period of 48-72 hours, classic symptoms of
nasal discharge, obstruction, sneezing, sore throat and cough. Myalgia and headache
may also be present. Fever is rare.
Diagnosis: based on symptoms (lack of fever combined with symptoms of localization
to the nasopharynx).
Prevention/Treatment: symptomatic- decongestants, antipyretics, fluids and bed rest.
Avoid infecting others, along with good hand washing, are best measures to prevent
spread.
Sinusitis
Aetiology: Acute sinusitis is most often a secondary response to a primary URT
infection of either a bacterial, viral or fungal nature. (Chronic sinusitis - lasts minimum 8
weeks, bacterial origin).
Pathogenesis: Impair ciliary action of epithelial lining of sinuses, increased mucous
secretions- obstruction and impedes drainage. With bacterial multiplication in the sinus
cavities, the mucus is converted to mucopurulent exudates. The pus further irritates the
mucosal lining causing more oedema, epithelial destruction and obstruction.
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Clinical Manifestations: The paranasal sinuses (commonly maxillary, ethmoid) are
implicated. Pain, sensation of pressure and tenderness over affected sinus exists.
Malaise and low-grade fever may occur.
Diagnosis: difficult to distinguish bacterial and viral sinusitis. If resolve within 10 days
most likely viral, if persist generally bacterial and antibiotics prescribed.
Pharyngitis
Aetiology: inflammation of the pharynx. Can be bacterial, viral (adenovirus, herpes
simplex virus, Epstein-Barr virus and cytomegalovirus infections) and less commonly
fungus.
Pathogenesis: viral pathogens invade the mucosal cells of the nasopharynx and oral
cavity, resulting in oedema and hyperemia of the mucous membranes and tonsils.
Clinical Manifestations: presents with a red, sore, scratchy throat. Inflammatory
exudate may cover tonsils. Vesicles or ulcers may be seen on the pharyngeal linings.
Depending on pathogen, fever and systemic manifestations such as malaise, myalgia, or
headache may present.
Diagnosis: Serologic tests may be used to confirm due to viral, mycoplasmal or
chlamydial pathogens.
Prevention/treatment: symptomatic treatment for viral pharyngitis. The exception is
herpes simplex virus, which can be treated with acyclovir if clinically warranted or if
diagnosed in immunocompromised patients.
Lower Respiratory Infections: Bronchitis, Bronchiolitis and Pneumonia.
Although viruses can cause lower respiratory tract infections, most LRI are of bacterial
aetiology.
Bronchitis and Bronchiolitis
Aetiology: respiratory syncytial virus primary cause in infants. Other viruses, including
influenza viruses and adenoviruses (as well as occasionally M pneumoniae) are also
implicated.
Pathogenesis: Infants initially have inflammation and sometimes necrosis of the
respiratory epithelium, with eventual sloughing. Bronchial and bronchiolar walls are
thickened. Exudate made up of necrotic material and respiratory secretions and the
narrowing of the bronchial lumen lead to airway obstruction.
Clinical Manifestations: bronchiolitis presents with a cough and fever is common. A
deepening cough, increased respiratory rate, and restlessness follow. Retractions of the
chest wall, nasal flaring, and grunting are prominent findings. Wheezing or actual lack of
breath sounds may be noted, respiratory failure and death may result.
Diagnosis: Aspirations of nasopharyngeal secretions or swabs are sufficient to obtain
specimens for viral culture in infants with bronchiolitis. Rapid serological diagnostic
tests for antibody or viral antigens may be performed on nasopharyngeal secretions.
Prevention/Treatment: Respiratory syncytial virus infections in infants may be
treated with ribavirin.
Pneumonia
inflammation of the lung parenchyma, consolidation of lung tissue may be identified by
physical examination and chest x-ray.
Aetiology: viral pneumonias are rare in healthy adults (exception of pneumonia caused
by influenza viruses). A serious complication following influenza virus infection is
secondary bacterial pneumonia, particularly s. pneumonia. Respiratory syncytial virus
can cause severe pneumonia among infants as well as among institutionalized adults.
Adenoviruses may also cause pneumonia. Measles pneumonia may occur in adults.
Pathogenesis and Clinical Manifestations: Infectious agents gain access to the lower
respiratory tract by the inhalation of aerosolized material, by aspiration of upper airway
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flora, or haematogenous seeding. Pneumonia occurs when lung defence mechanisms are
diminished or overwhelmed. The major symptoms or pneumonia are cough, chest pain,
fever, shortness of breath and sputum production. Patients are tachycardia. Headache,
confusion, abdominal pain, nausea, vomiting and diarrhoea may be present, depending
on the age of the patient and the organisms involved.
Microbiologic Diagnosis: Viral infection may be diagnosed by demonstration of
antigen in secretions or cultures or by an antibody response, or serologic tests.
Prevention/Treatment: Until organism identified, therapy based upon clinical history.
Therapy is then directed at the specific organism responsible.
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Antibiotics and antibacterial agents
Antibiotics:
'Biochemicals, originally of microbial origin [now including synthetic and semi-synthetic
compounds], that are capable, at low concentrations, of inhibiting the growth of
microorganisms'
– Macmillan Dictionary of Toxicology
NB: Antibiotics are released naturally into the soil by bacteria and fungi, but only came
to prominence in the medical sphere with the introduction of penicillin in 1941.
Other useful definitions:
Host
In our case, this is the patient. The organism harbouring the bacteria
Bactericidal
kills target pathogen
Such agents have a low minimal lethal concentration (MLC) i.e. they are effective at
relatively low concentrations that won't harm the host
Bacteriostatic
prevents growth only, and relies on the host's own resistance once treatment is stopped
These agents would only be cidal at much higher concentrations which would be
harmful to the host
Prokaryote - 'before the nucleus'
Bacteria, some algae and viruses
First cells to evolve on earth, 4 billion years ago.
Lack a nucleus or nuclear membrane - instead the DNA is just floating about
Eukaryote - 'true nucleus'
All multicellular, and some unicellular, organisms including fungi and HUMANS.
Defining factor is the presence of a nucleus, nuclear membrane and membrane-bound
organelles in the cells
1. Outline the major classes of antibiotics and antibacterial agents
Antibiotics can be classified in several ways. The most common method classifies them
according to their chemical structure as antibiotics sharing the same or similar chemical
structure will generally show similar patterns of antibacterial activity, effectiveness,
toxicity and allergic potential.
Penicillins
 β-Lactam ring
 Mechanism not fully understood
 1-5% US adults allergic
Cephalosporins
 β-Lactam ring (very similar to penicillin - see below)
 Originally isolated from Cephalosporum fungus
 Broad spectrum
 Inhibit petpidoglycan synthesis
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Tetracyclines
 4-ring stucture with variety of side chains
 semi-synthetic and naturally-occurring
 combine with ribosome subunit to inhibit protein synthesis
 bacteriostatic
Aminoglycosides
contain a cyclohexane ring + amino sugars
Bind to ribosome subunit
Bactericidal
Most effective against Gram-negative bacteria
Macrolides




Erythromycin is the most common one
12-22 carbon latone ring linked to sugars
Bacteriostatic
binds with rRNA of ribosomal subunit
inhibits peptide chain elongation during protein synthesis
Sulphonamides
 structurally analogous to metabolic compounds needed by bacteria
 compete with these compounds to inhibit them





Quinolones
 Contain 4-quinolone ring
 synthetic
 also a family of fluoroquinolones
 inhibit bacterial DNA gyrase or topoisomerase II
 broad-spectrum
Glycopeptides
 peptide linked to a disaccharide
 block peptidoglycan synthesis, specifically the transpeptidation step
 affects the cell wall
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2. Describe and classify their mechanisms of action according to the pathways and
processes which are affected
·
Interfering with bacterial cell wall
The most selective antibiotics will interfere with the synthesis of the bacterial cell wall,
they do this by:



inhibiting transpeptidation enzymes involved in the cross-linking of the
polysaccharide chains of the bacterial cell wall peptidoglycan.
activating the cell wall lytic enzymes and causing the wall to break down.
inhibiting cell wall synthesis by interfering with the action of the lipid
carrier that transports wall precursors across the plasma membrane
Inhibition of protein synthesis
Look back over your notes on protein synthesis to jog your memory about these processes.
The antibiotic agent binds to the bacterial ribosome. They attach to either the 30s
(small) subunit or the 50s (large) subunit of the bacterial ribosome.
The steps in protein synthesis that this can affect are:
 aminoacyl-tRNA binding
 peptide bond formation
 mRNA reading
 translocation
E.g. A) Erythromycin (a macrolide) binds to the rRNA of the 50s subunit and inhibits
peptide chain elongation during protein synthesis.
E.g. B) Aminoglycoside antibiotics bind to 30s subunit and interfere with protein
synthesis in two ways:
1. directly inhibit protein synthesis
2. cause misreading of the genetic code on the mRNA
Inhibition of nucleic acid synthesis
They achieve this through:
 Inhibiting bacterial DNA gyrase and thus interfere with DNA replication,
transcription and other activities
 Blocking RNA synthesis by binding to and inhibiting the DNA-dependent RNA
polymerase
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
This affects DNA replication and repair, and transcription as well as
chromosome separation
Damage to cell membranes
the antibiotic binds to the bacterial plasma membrane and disrupts its structure and
permeability properties
Antimetabolites
These antibiotics block metabolic pathways by competitively inhibiting the use of
metabolites by key enzymes.
For example, sulphonamides inhibit the folic acid metabolism of bacteria. Unlike
humans, who get it from their diet, most bacterial pathogens must synthesise folic acid.
The antibiotic competes with p-aminobenzoic acid for the active site of the enzyme
involved in folic acid synthesis, and the folate production decreases. Because it's so
important to their normal function, the bacterial growth will stop.
3. Identify the reasons for antibiotics being relatively less toxic to the host
The key to antibiotic efficacy is selective toxicity - the ability to kill or cease growth in
bacteria, but leave the host relatively unscathed.
The degree of selectivity depends on:
1. Therapeutic dose - the level required for clinical treatment
2. Toxic dose - the level at which it's too toxic for the host (also referred to as the
'breakpoint' in our lab)
The therapeutic index is the ratio of toxic dose: therapeutic dose, and the higher the
better. If the antibiotic damages the host cell, you get side effects.
The reason most antibiotics have very few side effects on the host is that they target
structures, processes and compounds found in prokaryotic or bacterial cells, and not in
eukaryotic or human cells.
E.g. Cell wall = defining character of prokaryotes. Therefore will not harm the host if it's
targeted
Folic acid synthesis = a process you won't find going on in human cells, therefore the
host isn't harmed when it's targeted
Less selective antibiotics will be less effective.
E.g. Antibiotics that target the cell membrane or nucleic acid synthesis will be less
effective, as the prokaryotic and eukaryotic nucleic acids are not very different, and the
same goes for the cell membrane structure
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Connective tissue LO’s
1) Know the basic composition of connective tissue
- Cells (permanent and wandering)
- Extracellular matrix (fibers, ground substance and tissue fluids)
Embryonic CT
CT Proper
Specialized CT
- mensenchyme
- Loose CT
- Adipose
- Mucous CT
- Dense CT; irregular
- Blood
and regular
- Bone
- Cartilage
- Haemopoetic tissue
- Lymphatic Tissue
2) Be able to demonstrate an understanding of the importance of
glycosaminoglycans (GAGS) in the function of the extracellular matrix.
- “Ground Substance consists of proteoglycans, very large macromolecules
composed of core protein to which glycoaminoglycans are covalently bound.”
- GAGS; long chain polysaccharides composed of repeating disaccharide units.
- Function; -ve chain high density so attracts water; this forms a hydrated gel
(hydration/storage of fluids).
- Allows diffusion of water-soluble small molecules but movement of large
molecules and bacteris is inhibited.
- GAGS has binding sites fro mnany growth factors.
- Examples of GAGS are Heparin, Keratin sulfate, dermatan and also the more
distinctive hyaluronic acid.
3) Identify the key cells and components of connective tissue and describe their
function.
- Cells; Fibroblasts, myogibroblsast, macrophages, adipose cells, mast cells,
mesenchyme calls,
- Permanent Components; Collagen fibers, reticular fibers, elastic fibers, ground
substances, -> viscous and clear.
- Wandering components ; Lymphocytes, plasma cells, neutrophils, Eosinophils,
Basophils, Monocytes.
4) Know the basic structure and function of the basement membrane in CT>
- Observed with H&E stain (Haemotoxylin and Eosin)  immediately adjacent to
CT, closely associated layer of collagen fibrils that belong the CT.
- Periodic acid-Schiff  isolates BM as a clear magenta dense layer between
epithelium and CT.
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Antibiotic Resistance
1. Briefly describe the consequences of antibiotic resistance at the individual and
population health levels
• If microbes in a patient develop antibiotic resistance, the antibiotic regime may not be
effective next time – meaning the infection may not be treatable next time, leading to an
infection causing serious illness or death
• 1968 – Dysentery epidemic (caused by Shigella) in Guatemala affected 112, 000 and
killed 12, 500. The strains responsible for this carried a resistance-plasmid containing
resistance to cloramphenicol, tetracycline, streptomycin and sulphonamide
• 1972 – Typhoid epidemic (caused by Salmonella typhi) in Mexico affected 100,000
and killed14,000 – with a drug resistance pattern the same as 1968 dysentery outbreak
• Worlwide, many strains of S. aureus are already resistant to all antibiotics except
vancomycin. Several cases of vancomycin-resistant S. aureus have been reported in US
and Japan. If full resistance achieved, it will be unstoppable killer.
• The impacts on the individual and population:
 Increased morbidity and mortality
 Increased length of hospital stay – leading to decreased bed availability and
increased expenses for government health budget
 Increased cost to patients (increased time off work, increased length of hospital
stay, increased expense of medications)
 Decreased protection from nosocomical infections (hospital acquired infections)
2. Outline measures to reduce its occurrence
• Vaccination is one of the most cost-effective methods of microbial disease prevention,
and bypasses the use of antibiotics
• Prevent inappropriate or excessive prescribing of antibiotics will not solve
problem, but will prevent it from worsening
 “It is estimated that over 50% of antibiotic prescriptions in hospital are given
without clear evidence of infection or adequate medical indication” (Prescott
2005)
• Renewed emphasis on prevention and control of infection – Improved sanitation,
isolation of infected patients and improved hygiene will reduce need for antibiotics
• Abolish use of antibiotics in animal food-source could decrease transfer of antibiotic
resistant genes from animals to humans – Up to 70% of animal food-source are given
antibiotics to mainly promote growth. More than 40% of antibiotics manufactured in
U.S. are given to animals
• Designing new drugs - In the 1980s pharmaceutical manufacturers, thinking
infectious diseases were essentially conquered, cut back severely on searching for
additional antibiotics. 3D drug modeling or gene sequencing of bacterial/fungal DNA
will help indentify new targets for drugs
• Using multiple drugs simultaneously in order to target all microbes, preventing one
strain thriving while others die
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“Consent and informed decision making”
1. Explain the ethical basis for obtaining consent to medical
treatment.
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Revolves around the principles of autonomy and self-determination.
Patient has right to choose what happens to his or her own body.
Each person has a right to bodily integrity to choose what occurs with
respect to his or her own body. ( Ref: “Marion’s Case” (1995) 172, CLR,
218-233 )
Revolves around the issues of patient autonomy and lf determination) 175 CLR 218 at 233
2. Describe the legal requirements for valid consent.
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Any procedure that involves intentional physical contact with a patient’s
body is an invasion of the patient’s bodily integrity and requires valid
consent.
No consent = Legal action for Assault & Battery
Medical practitioners have a legal duty to warn patients of the material
risk(s) of the proposed treatment
Failure to warn = Legal Action in Negligence
Patient needs enough information relative to their particular
circumstances to decide whether or not to undergo treatment.
Necessary Components – Consent must be:
•
•
•
•
Voluntary (no duress, pressure, coercion fraud, deceit or drugs)
By person with capacity
Procedure specific
Informed
Eg Dept Health and Ageing Immunisation Handbook 9th ed.
For consent to be legally valid, the following elements must be present:
 It must be given by a person with legal capacity, and of sufficient intellectual
capacity to understand the implications of being vaccinated.
 It must be given voluntarily.
 It can only be given after the relevant vaccine(s) and their potential risks and
benefits have been explained to the individual.
 The individual must have sufficient opportunity to seek further details or
explanations about the vaccine(s) and/or their administration.
3. List the exceptions to obtaining consent to medical treatment.

In circumstances where immediate treatment is necessary to save a
person’s life or to avert a serious and imminent threat (physical or
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mental), providing there is no unequivocal written direction by the
patient to the contrary;
If treatment has been authorised by order of a Court, for example, an
order of the Supreme Court regarding specific treatment for minor;
Procedures authorised by statute – such as compulsory blood, drug and
alcohol estimation on the request of a Police Officer;
Where a patient is unable to give consent, a guardian, a “person
responsible”, or the Guardianship Tribunal may be authorised to give
consent on behalf of the patient.
4. Explain the concepts of capacity and competence to consent and
provide examples of reduced capacity.
Capacity / Competence:
Must be able to process the information.
The patient must have:
•
•
•
•
An ability to take in and retain treatment information;
To believe it; and
To be able to assess the information, balancing the risks and
needs.
If no capacity to consent – the Guardianship Act 1987 may
apply.
Or: put another way - the patient must be aware of and have a general level of
understanding about the proposed procedure or treatment including associated
risks and side-effects.
Capacity/competency is also an issue when considering one’s right to refuse
treatment.
• Competent patients are entitled to refuse medical treatment, or
withdraw their consent to treatment.
➝ The High Court of Australia in Marion’s case held that a competent
person has the right “to choose what occurs with respect to his or her
own person” 1.
• Patients may not make logical or reasonable decisions, AND
• Refusal of treatment must be documented in the patient notes 1
Secretary, of Health and Community Services v JWB and SMB (1992) 175
CLR 218-58.
5. Describe the elements of effective communication required to
enable informed decision-making.
•
Informed decision making involves:-“A meaningful dialogue between
physician and
patient, instead of a unidirectional dutiful disclosure of alternatives, risks and
benefits by the physician1.”
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•
•
•
•
Delivery of clear, concise unambiguous information. Use plain language to
communicate information. Use interpreters when necessary. Ask questions
and discuss issues with a person close to them (with their permission).
Delivered in language appropriate to the age and interpretive ability of the
client.
Questioning of patient is encouraged to gauge level of understanding and
find out what is important to the patient. Give patients time to reflect on the
information. Questions should be answered as fully as possible. Check if
patient feels question has been answered.
The manner of delivering information may need to be modified if the patient
is too ill or badly injured to digest a detailed explanation.
Active consent involves both doctor and patient working together
towards the achievement of mutually agreed goals, given the material risks of the
situation and the expected outcome(s). From this perspective, the world of the doctorpatient
relationship is the world where the doctor provides an evidence-based
understanding of the risks of the procedure or intervention, and the patient provides the
basis for understanding which risks are of personal and material significance for him or
her.
6. Describe the requirements of provision of information and
disclosure of risks for medical procedures.

Need to inform patient of:
- Nature of condition
- Rationale for proposed treatment
- Risks (general, specific and material)*
- Alternatives
- Time involved, recovery period, follow-up care
- Costs
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*general risks = risks common to the type of procedure eg infection in
surgery;
specific risks = risks specific to the procedure eg gastric perforation in
lap banding;
material risks = risk relevant to the particular circumstances of the
individual patient.
The amount and level of information provided is proportional to the
chances of and degree of seriousness of the risks involved.
Complex interventions warrant more detailed explanation.
7. Explain what is meant by ‘material risk’ in the context of informed
decision making.
 material risks = risks relevant to the particular circumstances of the
individual patient.
o
Medical practitioners have a legal duty to warn patients of the material
risk(s) of the proposed treatment. Failure to warn = Legal Action in
Negligence
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o
o
Material risks – Rogers v Whitaker: (eye surgery that went badly – not
warned) A patient must be warned of all material risks before deciding
whether to receive treatment.
Courts adopt a patient centred approach.
ie : A risk is material if:
 In the circumstances of a particular case, a reasonable person in
the patient’s position, is warned of the risks, would be likely to attach
significance to it (OBJECTIVE TEST): OR
 The medical practitioner is, or should reasonably be, aware that
the particular patient, if warned of the risk, would be likely to
attach significance to it (SUBJECTIVE TEST).
Disclosing Material Risk:
• The disclosure of material risks will depend on:
– The nature of the risk.
– The nature of the intervention.
– Patient factors.
– Desire for information, questions asked.
– Temperament, attitude and level of understanding.
8. Describe the consequences of failure to obtain consent.
Background:
Criminal liability means the potential loss of freedom for breaking a law of the state
prohibiting certain conduct. Civil lliability is generally an order for money damages to be
paid to a private individual for a private wrong.
· Criminal laws are malum per se, meaning that it is against the moral principles of
society. They are normally punished with fines and/or loss of freedom through jail or
probation.
· Civil laws are malum prohibitum, meaning that they are against the law because
someone has said so. These are things like speeding and parking violations. They do not
result in loss of freedom, though they can result in loss of privilages or fines.
Criminal or civil liability may occur where medical treatment is delivered without
his/her consent.
•
•
•
•
Assault: Conduct that causes a person to apprehend the infliction of bodily
harm.
Assault: A practitioner may be found to have committed assault if the patient
is touched or physically examined without consent. This may extend to
assault occasioning actual bodily harm (S59 Crimes Act, 1900) where such
treatment results in physical or psychological harm.
In addition, a medical practitioner could be liable for the common law
offence of false imprisonment, if it can be proved that in treating the patient
without consent, the medical practitioner unlawfully restrained the patient’s
liberty or freedom of movement.
Tort of trespass to the body
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•
•
Battery – act of one person which causes some physical contact with another
person. Any unauthorised contact may constitute battery – even without
hostile intent. Comes down to legally valid consent being sought and gained
before examining or laying hands on a patient.
Would include detailing what you are going to examine and specifically how
you are going to examine. The more invasive or intimate the situation is
should dictate how specifically and in what detail you deliver the
information.
Medical Boards may discipline practitioners failing to gain consent.
9. Describe the consequences of failure to provide information and
disclose the risks of a medical procedure.
•
•
•
•
Goes to the issue of “informed” when looking at consent.
Action in negligence can result from failure to obtain informed consent.
Action in negligence is to be contrasted to action in trespass.
Based on failure to obtain a patient’s informed consent, which requires
medical practitioners to disclose more information to the patient, in
particular, any material risk of the proposed treatment.
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Hypotheses of Disease Causation:
1. Examine theories of proving hypotheses & disease causation. (History &
Philosophy of Science &Medicine).
Sir Bradford Hill: nine criteria for causation, outlining the minimal conditions needed to
establish a causal relationship between two items.
1. Strength of the association. How large is the effect? This is defined by the size
of the association as measured by appropriate statistical tests. The stronger the
association, the more likely it is that the relation of "A" to "B" is causal.
2. The consistency of the association. Has the same association been observed
by others, in different populations, using a different method? The association is
consistent when results are replicated in studies in different settings using
different methods. That is, if a relationship is causal, we would expect to find it
consistently in different studies and in different populations. This is why
numerous experiments have to be done before meaningful statements can be
made about the causal relationship between two or more factors
3. Specificity. Does altering only the cause alter the effect? This is established
when a single putative cause produces a specific effect. Can be determined if
altering only the cause alters the effect.
4. Temporal relationship. Does the cause precede the effect? Exposure always
precedes the outcome. If factor "A" is believed to cause a disease, then it is clear
that factor "A" must necessarily always precede the occurrence of the disease.
5. Biological gradient. Is there a dose response? An increasing amount of
exposure increases the risk. If a dose-response relationship is present, it is
strong evidence for a causal relationship
6. Biological plausibility. Does it make sense? The association agrees with
currently accepted understanding of pathological processes. In other words,
there needs to be some theoretical basis for positing an association between a
vector and disease, or one social phenomenon and another.
7. Coherence. Does the evidence fit with what is known regarding the natural
history and biology of the outcome? The association should be compatible with
existing theory and knowledge. In other words, it is necessary to evaluate claims
of causality within the context of the current state of knowledge within a given
field and in related fields.
8. Experimental evidence. Are there any clinical studies supporting the
association and can the condition be altered (prevented or ameliorated) by an
appropriate experimental regimen?
9. Reasoning by analogy. Is the observed association supported by similar
associations? In judging whether a reported association is causal, it is necessary
to determine the extent to which researchers have taken other possible
explanations into account and have effectively ruled out such alternate
explanations. In other words, it is always necessary to consider multiple
hypotheses before making conclusions about the causal relationship between
any two items under investigation.
Historically speaking, discussions of causal criteria arose from the recognised
limitations of the Henle-Koch postulates, formalised in the late 19th century to establish
causation for infectious agents. These postulates required the causal factor to be
necessary and present, applied only to a subset of infectious organisms, and conflict
with multifactorial causal explanations. The non-specificity of causal agents was of
particular concern Two lists of criteria published before 1960 did not include specificity,
and instead included consistency and replication, strength, dose-response,
Week 5 Magic Bullets
experimentation, temporality and biological reasonableness. The term ‘criteria for
causation’ applied to Hill’s list of factors to consider before inferring causation from an
observed association. Hill himself however never called these considerations criteria,
but rather referred to them as viewpoints and never saw them as the ‘hard-and-fast’
rules of evidence. Nevertheless, the publication of his landmark address to the Royal
Society of Medicine is frequently cited as the authorative source for causal criteria in
epidemiological practice.
2. Compare and contrast an evidence based medicine approach to disease
causation with alternate theories which may be held by patients. Use
immunisation as an example of this.
Evidence Based Medicine (EBM) is the "conscientious, explicit and judicious use of
current best evidence in making decisions about the care of individual patients. The
practice of evidence based medicine means integrating individual clinical expertise with
the best available external clinical evidence from systematic research." EBM is a
movement which aims to increase the use of high quality clinical research in clinical
decision making.
EBM/EBP recognizes that many aspects of health care depend on individual factors such
as quality and vol judgments, which are only partially subject to scientific methods. EBP,
however, seeks to clarify those parts of medical practice that are in principle subject to
scientific methods and to apply these methods to ensure the best prediction of outcomes
in medical treatment, finding out what the patient wants to know and the best possible
evidence on which to base answers.
Alternative medicine can be seen as any healing practice that does not fall within the
realm of conventional medicine or treatments shown not to always be consistently to be
effective.
Traditional Chinese medicine has been practiced for over 3000 years and over one
quarter of the world's population now uses one or more of its component therapies.
It combines the use of medicinal herbs, acupuncture, and the use of therapeutic
exercises such as Qi Gong. It has proven to be effective in the treatment of many chronic
diseases including cancer, allergies, heart disease and AIDS. TCM takes a personalised
look at the patient and corrects the underlying causes of imbalance and patterns of
disharmony, thus taking a holistic approach.
Homeopathy is a non-toxic health care system now used by hundreds of millions of
people around the world. An excellent first-aid system and is also superb in the
treatment of minor ailments such as earaches, the common cold, and flu. Homeopathy is
again based on the treatment of the individual and when used by a knowledgeable
practitioner can also be very effective in the cure of conditions such as hay fever,
digestive problems, rheumatoid arthritis, and respiratory infections.
Naturopathic medicine also strongly believes in the body's inherent ability to heal itself.
Naturopathy emphasizes the need for seeking and treating the causes of a disease rather
than simply suppressing its symptoms. Naturopaths use dietary modifications, herbal
medicines, homeopathy, acupuncture, hydrotherapy, massage, and lifestyle counseling
to achieve healing.
In terms of immunisation:
-immunisation is essentially implemented by Governments and Doctors to which the
patient feels they have no autonomy or part in aiding their health.
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-immunisation is viewed as the use of chemicals and foreign, potentially harmful
substances into the body.
-immunisations are a general, common, mass made product that can have different side
affects for different people.
3. Identify and discuss ethical issues in immunisation.
Reason people vaccinate
(Some of these reasons also follow into reasons why people do/do not consent for other
medical procedures)
 Anticipatory regret  “I will never forgive myself if something went wrong
 Band wagoning  Other people do it, therefore I will do the same
 Omission bias ‘Feel bad if my failure to do something causes a detrimental
outcome to someone else
 Availability heuristic  ‘I just know that it will happen to me, therefore I need to
have this done’
 Altruism  ‘I want to protect others’
 ‘recommended’  guidelines say so, therefore I should
 Want immunity
 Required by schools, childcare centres
 Financial incentives/work/employment requirements
Reason people don’t vaccinate
 Adverse reactions  often given excessive media coverage such as flu injection
last year, the recent case of ‘Tourette’s like symptoms in the US, groups that
argue there is a link between the MMR vaccine and autism (google Jenny
McCarthy website)
 Optimism bias  ‘It won’t happen to me, therefore it is unnecessary’
 Ambiguity aversion  too much uncertainty, therefore rather not elect
procedure
 Prefer natural alternatives
 Preference to receive immunity by contracting the disease (in the case of the pox
party)
 Preference to go ‘against the trend’
 Don’t know the importance (eg whopping cough)
 Presume that if vaccinated as child, then covered (eg: tb)
 Cost
 Belief that “I will get the disease if vaccinated “measles vaccine causes measles”
 Immunisation is not responsible for the decline in communicable diseases;
rather improved sanitation, nutrition etc
Risk versus benefit
The overall risks outweight the benefits further a majority of the risks include minor
and limited local irritation and fever. Most people over emphasise the risks associated
with vaccinations and underplay those related to catching the actual disease.
Relates to the fear of commission compared with omission; side effects from
vaccinations is directly from the parents actions whilst obtaining a disease has no level
of blame on parents.
Public health and paternalism
In this process a foreign material is injected into an individual hence compelling one to
be immunised against their will and therefore can constitute assault
Herd immunity and paradox of free riders
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Herd immunity is whereby once a critical proportion of a population is immune to a
particular disease the disease can no longer circulate through the community. The
implication of herd immunity is that if children are not immunised this will not only
make them susceptible to infection but also increase risk for others not yet able to be
vaccinated. Free riders are parents who live in a highly immunised population and elect
not to immunise their children and thus rely on protection of the herd.
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Measuring Disease Frequency and Association
1. Define prevalence and incidence and discuss the relationship between these
measures
How does epidemiology describe disease?
Incidence
How frequently do new cases occur?
The incidence rate provides us with a standardised measure, allowing comparison
across populations and the testing of hypotheses. It takes into account the population
size, and the duration of exposure - it reflects the true magnitude of the disease in the
population. It seems there are quite a few meanings and terms used in different ways.
Our lecturer described incidence thus:
 Incidence is a measure of the FREQUENCY of new cases occurring
 Incidence reflects the pathology of the disease, i.e. a fast-onset disease would
have a higher frequency in a defined period than a slow-developing disease
There are two types of incidence:
1. Cumulative incidence (incidence)
2. Incidence rate (incidence density)
Cumulative incidence (CI)
no. of people who get the disease over a certain period
÷
no. of individuals in the population at the beginning of the period
Incidence rate (IR)
no. of people who get the disease over a certain period
÷
number of person-time when people were at risk of developing the disease
The lecturer used the example of students developing glandular fever during their first
semester, as follows:
50 students enroll, 5 with a history of GF
During semester 1, 5 develop GF
No drop outs
Once infected with glandular fever, you have lifelong immunity
number of persons who develop the disease over time period
÷
average number of people–time they were at risk of developing the disease
over same period
numerator: 5 developed the disease
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Denominator: (average number of people at risk) 45 at beginning of semester, and at
the end of semester it’s only 40. So the average of the two is 42.5
Now add the time factor:
Full semester = 10 weeks
42.5 x 10 weeks = 425 person-time average
The incidence rate of glandular fever = 5/425 = 0.012/person-weeks
Remember: IR = Figure per person-time (month, year, day etc.)
Sometimes you’ll see it as a percentage.
Prevalence
The amount of disease in a population at a given point in time
Prevalence reflects the burden of disease in a population at a single point in time, i.e. the
proportion of the population who actually have the disease at that instant. It can show
us what the most common disease is in a population, and it is used to assess the impact
of disease on public health.
number of people who have the disease at time t
÷
total number of people in the population at time t
It's expressed as a rate, either as a percentage or per thousand.
E.g. the glandular fever scenario:
The prevalence of glandular fever is 5 out of 50 = 10% = 100/1000
Prevalence can be divided into two categories:
 Point prevalence - at a single point in time e.g. on 1/1/12
 Period prevalence - from one point in time to another e.g. from 1/1/12 - 3/1/12
The relationship between incidence and prevalence
Prevalence measures the existing disease, while incidence measures the rate at which
new cases of the disease occur.
Prevalence depends on
 the frequency of new cases
 duration of the disease
 population movement
prevalence diagram.docx
27.3 KB
Week 5 Magic Bullets
If incidence increases, so will prevalence (in general - This assumes a static population,
however, and a prevalence of 10% or less)
Ponder this:
If you find a treatment for the disease which means it's no longer fatal, the prevalence
will increase because people are no longer dying from the disease, resulting in a higher
number of people with the disease in the population
However if you find a cure the prevalence will decrease since you've got rid of the
disease from the population
2. Identify and interpret measures of association used to describe the relationship
between exposure and outcome in epidemiological studies
How does epidemiology identify the cause of disease?
In order to identify the cause of a disease, we measure the association
Association = statistical relationship between two events or characteristics
in epidemiology, the association = relationship between exposure and disease
Relationship does not imply causation
The relationship between cause and effect when we're looking at EXPOSURE
Measures of association:
Absolute measures: Difference measurement
Relative measures: Risk ratios (RR) and odds ratios (OR)
The difference between these measurements is illustrated with an example:
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The absolute risk difference between men and women developing a myocardial
infarction is
5 cases/1000/year in males - 1 case/1000/year in females = 4 cases/1000/year
The relative risk of myocardial infarction in men compared with women is
5 cases/1000/year in males ÷ 1 case/1000/year in females = 5
1. Difference measures
E.g. Attributable risk = risk (exposed) – risk (unexposed)
The attributable risk shows the difference in incidence rates between exposed and nonexposed
AR<1
cases are less likely to have been exposed
likely to have been exposed
AR=1
AR>1
exposure has no effect on likelihood of disease
cases are more
2. Relative risk
Relative risk =
measure of disease in the 'exposed population'
÷
measure of the disease in the 'unexposed population'
This shows the risk that exposure will have on the outcome
RR<1
exposure DECREASES likelihood of disease
likelihood of disease
NEGATIVE association
exposure provides protection
RR=1
exposure has no effect on likelihood of disease
NO association
RR>1
exposure increases
POSITIVE association
3. Odds ratio
Used as an estimate of risk when disease is rare, and difficult to find in the population
Odds ratio =
OR<1
Odds of exposure in 'cases'
÷
odds of exposure in 'non-cases'
cases are less likely to have been exposed
have been exposed
OR=1
exposure has no effect on likelihood of disease
OR>1
cases are more likely to
Week 5 Magic Bullets
Communication skills
IDENTIFY AND PRACTICE THE COMMUNICATION SKILLS REQUIRED TO ESTABLISH RAPPORT
Why establish rapport?
 It is important to try to put the patient at ease immediately, because unless a
rapport is established, the history taking is likely to be unrewarding
 The treatment of a patient begins the moment one reaches the beside/ the
patient enters the consulting rooms
 The patient’s first impressions of a doctor’s professional manner will have a
lasting effect
 As a doctor (or a medical student in training) you should aim to leave the patient
feeling better for their visit
How do you establish good rapport?
 Make a deliberate point of introducing yourself
 Make a deliberate point of explaining your role. Eg: “Good afternoon, Mrs. Smith.
My name is Jess Quinn. I am Dr. Fotheringham’s medical student.”
 Offer the patient a seat
 Ensure privacy
 Sit near the patient close to eye level
 Address the patient respectfully
DISCUSS STRATEGIES FOR EFFECTIVE COMMUNICATION WITH PATIENTS
 As above
 In addition – as part of taking patient history, ensure to ask patient what concern
has brought them to see doctor today, don’t just make presumption (patientfocussed interview vs. doctor focussed interview)
 Interview in careful and logical manner
 Listen carefully
 Ask questions when appropriately (do not ask questions that patient has already
answered – appears that patient has not been listened to)
 Note non-verbal clues
 Correctly interpret information obtained
IDENTIFY WHAT YOU NEED TO KNOW WHEN INTERVIEWING AND EXAMINING PATIENTS
 This depends on exactly what patient complaint it, however a general overview
at this stage is:
o Presenting symptom
o History of presenting illness
o Past history
o Social history
o Family history
o Systems review
DEMONSTRATE THE USE OF APPROPRIATE COMMUNICATION SKILLS IN ELICITING A MEDICAL HISTORY

Time for some CCS practice!!
Week 5 Magic Bullets