Week 7 Infections On Surfaces/ Allergy

Question 1

Describe the range of normal microbiota

Answer 1

Mocosal flora

Question 2

What is a surface?

Answer 2

Interface between a solid and either a liquid or gas

Question 3

How do people get infections?

Answer 3

• Invasion- strep pyogenes pharyngitis
• Migration- E. coli UTI
• Inoculation- coagulase negative staphylococcus prosthetic joint infection
• haematogenous- virions strep endocarditis- circulates from mouth to bloodstream then to valves- if damaged sticks and multiples

Question 4

What are surface infections important?

Answer 4

Produce biofilms which protect the bacteria from host and AB attack

Question 5

Describe the ‘patient’ surfaces from the infection model?

Answer 5

Surfaces:
Skin- epithelium, hair, nails
Mucosal surfaces- conjunctiva, gastrointestinal- H pylori- peptic ulcers and cancers, respiratory, genitourinary

Question 6

Describe biofilm formation- 8 steps

Answer 6

1. Starvation of bacteria= shrink, spore like called ultramicrobacteria-> wait in soil, rock, tissue until suitable conditions for growth
2. Active bacteria attach to anything- change in gene expression- swimmers to stickers
3. Attached bacteria multiply, encase colonies within slimy matrix
4. Nutrients diffuse int matrix
5. Close proximity of cells in matrix aids exchange of molecular signals that regulate behaviouri
6. Chemical gradients creates micro environments for different species or levels of activity
7. Antimicrobials damage outer cell layers but biofilm community resistant
8. Aggregated cells can detach or roll or ripple along a surface in sheets, remaining in protected biofilm state - can embolise- block small blood vessels- necrotic tissue- release nutrients allowing bacteria to grow= multiple abscesses- common on brain from endocarditis

Question 7

What is quorum sensing, what does it control and what are the 3 principles?

Answer 7

communication between bacteria- bacteria actively secrete molecules into environment then sense how much is out there- from themselves and possibly other bacteria- stimulate biofilm formation together by coordinate gene expression according to the density of their local population.
It controls- sporulation, biofilm formation, virulence factor secretion
Three principles
- signalling molecules- autoinducers (AI)
- cell surface or cytoplasmic receptors
- gene expression-> co operative behaviours and more AI production

Question 8

Give some examples of natural surface infections- internal and external?

Answer 8

External- cellulitis- can lead to sepsis- staph aureus in blood, pharyngitis, conjunctivitis, gastroenteritis, UTI, pneumonia in alveoli
Internal- endovascular (endocarditis (valves), vasculitis (vessels)), septic arthritis (joints- spongey bone interacting with bloodstream), osteomyelitis, empyema (between 2 pleural lining)

Question 9

Give some examples of prosthetic surface infection?

Answer 9

• Intravascular lines- venflon- if left to long bacteria on skin move to plastic- set up local infection- tract along veins and can=systemic infection if enters bloodstream, central lines- bigger and longer use so more chance of infection, hickman line- cancer burried subcutaneously as need high blood flow to dilute
• peritoneal dialysis catheters, prosthetic joints, cardiac valves, pacing wires, endovascular grafts, ventriculo- peritoneal shunts

Question 10

What are some common skin microorganisms- viruses, bacteria, fungi and parasites?

Answer 10

• Viruses- papilloma (warts), herpes simplex
• Gram +ve bacteria- staph aureus (1/3carry it), coagulate negative staphylococci (all carrying), corynebacterium
• gram -ve bacteria- enterobacteriaceae- coliforms= ecoli, klebsiella pneumonia- facultative aerobes- lactose fermenting for energy source- in L bowel and skin
• Fungi- yeast, dermatophytes (athletes foot, ringworm)
• parasites- mites

Question 11

How do microorganisms cause disease?

Answer 11

Virulence factors
- exotoxins- cytolytic, AB toxins, superantigens, enzymes
- endotoxins 
Host cellular damage
- direct
- consequent to host immune response

Question 12

What is the difference in causes of prosthetic valve endocarditis >1 year and

Answer 12

> 1 year viridans streptococci, enterococcus faecalis, staph aureus (bloodstream infection), HACEK group, candida

Question 13

How are surface infections treated?

Answer 13

Aim- sterilise tissue, reduce bioburden
Antibacterial soap
Remove prosthetic material
Surgery- respect infected material
Challenges- poor AB penetration of biofilm, low metabolic activity of biofilm microorganisms, dangers/ difficulties of surgery

Question 14

How are surface infections prevented- 3 natural and prosthetic?

Answer 14

Natural surfaces- maintain surface integrity, prevent bacterial surface colonisation, remove colonising bacteria
Prosthetic surfaces- prevent contamination, inhibit surface colonisation, remove colonising bacteria

Question 15

What are the common causative organisms of prosthetic joint infections and cardiac pacing wire endocarditis?

Answer 15

Both - Coagulase negative staphylococci, staphylococcus aureus

Question 16

Name the important steps in allergic reactions starting with trigger- use example of beesting?

Answer 16

Trigger eg. bee sting,
timing before symptoms- shortly after sting,
symptoms- resp- wheezy, difficulty breathing, cardio- lightheaded BP 80/40, skin- rash, face- swollen
Therapy- IM of epinephrine
Outcome-death
Why? - had been stung 2 yrs ago- local reaction only

Question 17

What is the pathogenesis of infections on a surface?

Answer 17

Adherence to host cells or prosthetic surface- pili or fimbriae
Biofilm formation
Invasion and multiplication
Host response- pyogenic (neutrophils-> pus), granulomatous (fibroblasts, lymphocytes, macrophages-> modular inflammatory lesions)

Question 18

How are surface infections diagnosed?

Answer 18

Diagnosis

• identify organism and its Antimicrobial susceptibility
• challenges- adherent organisms, low metabolic state/small colony variants
• blood cultures
• tissue/ prosthetic material sonics toon and culture

Question 19

how does prosthetic valve endocarditis come about?

Answer 19

turbulent blood flow across valve- peel off endothelium
poor oral hygiene- bacteria from mouth to bloodstream- usually removed by phagocytes and spleen- if settles on sub-endothelial tissue around valve= infection

Question 20

What are the different types of hypersensitivity reactions?

Answer 20

type 1- immediate

Question 21

What is hypersensitivity?

Answer 21

Antigen specific immune responses that are either inappropriate or excessive and that result in damage to host

Question 22

What are the two stages of hypersensitivity reactions?

Answer 22

Sensitisation phase- first encounter with antigen- immune response driven, keeps memory of it but is a silence response
Effector phage- clinical pathology upon re- exposure with SAME antigen

Question 23

What is microbiota?

Answer 23

Commensals- microorganisms carried on skin and mucosal surfaces- normally harmless or even beneficial, harmful if transfer to other sites

Question 23

what are the different types of hypersensitivity reactions- time, mediators, process?

Answer 23

type 1- immediate

Question 24

What is the significance of TH1 and TH2 phenotype in relation to allergies?

Answer 24

Born with TH2 phenotype- favoured in developed countries- IgE production Want TH1 as this is correct immune response- develops in children growing up in developing countries

Question 25

How can different childhoods affect likelihood of having allergies?

Answer 25

Exposure at a young age to allergens and infective microbes would make immune system enter protective stage- more likely to be protected against allergies - Developing countries where less use of ABs, rural homes, in contact with livestock, poor sanitation and with large family sizes are less likely to have allergies.

Question 26

What are some of the most common allergens?

Answer 26

``` House dust mites, animals, Tree and grass pollen Insect venom- wasps and bee stings Medications- penicillin Chemicals- latex Foods- peanuts, milk ```

Question 27

Explain Clinical cross- reactivity

Answer 27

Allergies to certain things increase risk of allergies to other things Different allergens have same proteins that share same homology Eg cows milk and goats milk, shellfish and other shellfish

Question 28

Which cells are involved in allergic reactions- what is driving it?

Answer 28

Mast cells- big nucleus and cytoplasm Has many different granules containing different mediators driving alleged responses Are close to blood vessels and present on all mucosal surfaces- GI and resp symptoms - regulate acute and early phases of inflammation - all granules released near blood vessels

Question 29

What are some important Mast cell mediators in acute reactions

Answer 29

toxic mediators- prostaglandins Histamine and heparin | lipid mediators- leukotrienes C4, D4 and E4, and platelet activating actor

Question 30

describe the immune mechanisms of allergic reaction- 1st and 2nd encounters

Answer 30

1st encounter sensitisation to allergen - IgE produced but no symptoms 2nd encounter- Cross linking of IgE- mass cells- activate it and triggers release of granules containing- histamine, chemokines and the synthesis of new mediators- leukotrienes and prostaglandins - increased vascular permeability - vasodilation- loss of fluid - Act of muscle in lungs- bronchoconstriction

Question 31

Describe the manifestations of allergic reactions in the skin- dermis and epidermis

Answer 31

mast cells in the epidermis- urticaria | mast cell in deep dermis- angioedema- fluid going into tissue- lips,, eyes, tongue, and Upper resp tract

Question 32

How do you treat anaphylactic shock and how does this work?

Answer 32

Epinephrine (adrenaline) intramuscular - Reverse peripheral vasodilation and reduces oedema and alleviate hypotension - Reverse airway obstruction/bronchospasm- bronchodilation - Increase force of myocardial contraction - Inhibits mast cell activation TREATMENT NEEDS TO BE GIVEN IMMEDIATELY

Question 33

What are some of the key points about epinephrine?

Answer 33

Timesaver- lifesaver IM not SC Biphasic reaction- Will be second anaphylaxis phases triggered without allergen- multiple doses may be needed- should carry 2 epipens

Question 34

What are some of the common allergic diseases- allergens, route of entry, response?

Answer 34

- Systemic anaphylaxis- drugs, serum, peanuts- IV entry- oedema, increased vascular permeability, circulatory collapse - Acute urticaria- animal hair, insect bites- through skin- local increase in blood flow and vascular permeability - Allergic rhinitis (hey fever)- pollens, dust- inhalation- oedema of nasal mucosa - Asthma- animal danders, pollen- inhalation- bronchiocontriction, >mucus, airway inflammation Food allergy- nuts, milk, eggs- oral route- vomiting, diarrhoea

Question 35

what are biofilms and how are they beneficial to bacteria?

Answer 35

any group of microorganisms where cells stick to each other on a surface- frequently embedded within a self-produced matrix of extracellular polymeric substance (EPS)- mucopolysaccharides produced and secreted- contains extracellular DNA, proteins, and polysaccharides- creates 3D extracellular biofilm membrane over top - helps bacteria adhere and protects them from host macrophages, complement and ABs- cannot penetrate film

Question 36

How are allergies diagnosed?

Answer 36

- Clinical history- what driving response (atrophy)- is it there all year- seasonality, route of exposure - blood tests- stages of sensitisation- serum allergen- specific IgE Serum mast cell tryptase, histamine- systemic degranulation - Skin prick test- range of allergens- wheal and flare reaction - challenge test- food and drug allergy - risk of anaphylaxis

Question 37

What are some of the common signs of anaphylaxis?

Answer 37

Involves more than 1 system- - CNS- lightheadedness, loss of consciousness, confusion, headache, anxiety - Resp- SOB, wheezy, hoarseness, pain swallowing, cough - GI- crampy abdo, diarrhoea, vomiting - skin- hives, itchiness, flushing - Heart and vasculature- fast or slow HR, low BP swelling of lips, runny nose

Question 38

What are the systemic manifestations of allergic reaction- anaphylaxis?

Answer 38

Systemic absorption and reaction to allergen- insect, venom = systemic activation of mast cells = hypotension, cardiovascular collapse, generalised urticaria, angioedema, breathing problems

Question 38

what is involved in the management of allergy?

Answer 38

- allergen avoidance/elimination- read food labels, house dust mite avoidance, avoid high risk situations - education- parents recognise symps, correct use of epipen, call 999 when epipen used- often needs to be used more than once - medic alert identification - drugs- anti histamines, corticosteroids, anti IgE IgG (omalizumab), anaphylaxis- inject adrenaline - allergen desensitization- pt with high risk of systemic attacks

Question 39

what is allergen desensitisation?

Answer 39

administration of increasing doses of allergen extracts over a period of years- given to pts by injection or drops/tabs under tongue- sublingual 99% effective in pts with bee and wasp venom anaphylaxis

Question 39

what are some possible mechanisms of allergen desesitisation?

Answer 39

shift from TH2 to TH1 | allergen specific blocking IgG