Infection Session 3 Flashcards

1
Q

How is Neisseria meningitidis transmitted?

A

Direct contact w/respiratory secretions

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2
Q

What three consequences can result due to Neisseria meningitidis introduction to a new host?

A

Removed
Asymptomatic carrier - part of resp tract flora
Rapidly progressive disease

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3
Q

What causes a purpuric rash?

A

Small bleeding vessels near skin surface

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4
Q

How is a blanching purpuric rash differentiated from a non-blanching one?

A

Blanching: red spots disappear when pressure is applied

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5
Q

What is Systemic Inflammatory Response Syndrome (SIRS)?

A
A response to non-specific insult with 2 or more of:
Temp 38
HR > 90 bpm
RR >20
WBC 12x10^9
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6
Q

What is bacteraemia?

A

Presence of bacteria in the blood +/- clinical features

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7
Q

What is septicaemia?

A

Clinical term for generalised sepsis where the pt is physiologically unwell

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8
Q

What is severe sepsis?

A

SIRS + organ dysfunction/hypoperfusion

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9
Q

How can severe sepsis be identified after SIRS has been detected?

A

Hypotension

Decreased urine output (measure creatinine and urea)

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10
Q

What is sepsis?

A

Systemic response to infection - SIRS + infection

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11
Q

Does the infection in sepsis have to be confirmed?

A

No, it can be suspected and still qualify

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12
Q

What is septic shock?

A

Severe sepsis + persistent low BP despite IV fluid administration in the ‘golden hour’

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13
Q

What classification forw Neisseria meningitidis fit into?

A

G-ve diplococci

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14
Q

What virulence factors are present in the meningococcus structure?

A

Lipopolysaccharide endotoxin
Pili
Polysaccharide capsule

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15
Q

What is the function of the polysaccharide capsule in the meningococcus structure?

A

Promote adherence
Prevent phagocytosis
Capsular antigen defines serogroup

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16
Q

What happens in the inflammatory cascade?

A

Endotoxin binds to macrophages –> local cytokine release for inflammatory response and RES activation –> systemic cytokine release for homeostasis –> homeostasis not restored = SIRS

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17
Q

What causes circulatory insult in the inflammatory cascade?

A

Cytokines causing humoral cascades and RES activation

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18
Q

What is stimulated by systemic release of cytokines in the inflammatory cascade?

A

GF
Macrophages
Platelets

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19
Q

How do cytokines promote coagulation?

A

Initiate production of thrombin and inhibit fibrinolysis

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20
Q

Why is microvascular injury in the inflammatory cascade a major cause of shock and multi-organ failure?

A

Promotion of coagulation –> microvascular thrombosis –> progressive necrosis, organ ischaemia, dysfunction and failure

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21
Q

What urgent investigations should be conducted to assess the physiological state of a pt with acute sepsis?

A
FBC
U&Es
PCR
Blood sugar
CRP
Clotting studies
ABG
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22
Q

What are the steps in Sepsis 6?

A
  1. Deliver high-flow oxygen
  2. Blood cultures (consider source control)
  3. Empirical IV Abx
  4. Serum lactate
  5. IV fluids
  6. Start accurate urine output measurement
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23
Q

When should Sepsis 6 be performed?

A

Within 1 hour of identification of sepsis

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24
Q

What life-threatening complications can occur w/in hours of presentation in bacterial meningitis?

A
Irreversible hypotension
Respiratory failure
AKI
Increased intracranial pressure
Ischaemic necrosis of periphery
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25
Q

Why is an increase in intracranial pressure in meningitis a contraindication for lumbar puncture to investigate the causative agent?

A

Pressure changes would result in coning –> death

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26
Q

How is a diagnosis of bacterial meningitis confirmed?

A

PCR and culture of blood and CSF (if safe)

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27
Q

What is investigated when looking at a CSF sample in the lab?

A
Glucose
Protein
Turbidity
Colour
WBCs
RBCs
Gram stain
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28
Q

When choosing an empirical Abx for bacterial meningitis, what should be considered?

A

Most likely causative agent for relevant age group

Can it penetrate CSF?

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29
Q

What does taking a serum lactate in the Sepsis 6 pathway identify?

A

Acute metabolic derangement

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30
Q

What action should follow a diagnosis of bacterial meningitis once the pt is stable?

A

Notify local Health Protection Unit

Offer prophylactic Abx to pt contacts immediately

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31
Q

Generally how does viral meningitis differ from bacterial?

A

Viral is more common but less severe

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32
Q

What is the immune system?

A

Cells and organs that contribute to immune defences against infectious and non-infectious conditions

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33
Q

When are threatening self-cells pathogenic?

A

Autoimmune disease

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34
Q

Define infectious disease.

A

When a pathogen succeeds in evading and/or overwhelming the host’s immune defences

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35
Q

How does the immune system recognise pathogens?

A

Cell surface receptors on innate and adaptive immune cells

Soluble receptors in complement

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36
Q

Why must the immune system regulate itself?

A

To minimise damage to the host by resolution so that when the infection stops the inflammation/immune response stops too

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37
Q

What are the four roles of the immune system?

A

Pathogen recognition
Containing/eliminating the infection
Self-regulation
Remembering pathogens

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38
Q

Compare and contrast innate and adaptive immunity.

A

Innate: immediate protection (secs), lacks specificity, memory and variable intensity
Adaptive: slow (1-3 days), can distinguish b/w strains and epitopes and has memory and variable intensity

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39
Q

Which immune response allows for human survival?

A

Adaptive

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40
Q

List some physical barriers to infection in the innate immune system.

A

Skin
Mucous membranes
Bronchial cilia

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41
Q

List some physiological barriers to infection in the innate immune system.

A

Diarrhoea
Vomiting
Coughing
Sneezing

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42
Q

Are physiological barriers to infection unique to infection?

A

No, seen in allergy too

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43
Q

List some chemical barriers to infection in the innate immune system.

A

Low pH of skin, stomach and vagina
Antimicrobial molecules (e.g. IgA) in tears, saliva and mucous membranes
Lysozymes in secretions

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44
Q

What is made by mucosa and epithelium to interfere with attachment of pathogens?

A

Beta-defensins

45
Q

Why are non-pathogenic microbes strategically placed at potential locations of entry of pathogens into the body?

A

Compete for attachment sites and resources

Produce antimicrobial chemicals

46
Q

What are biological barriers to infection in the innate immune system?

A

Non-pathogenic microbes at strategic locations

47
Q

What vitamins do non-pathogenic microbes in the body synthesise?

A

K, B12 and other B vitamins

48
Q

Are non-pathogenic microbes found in internal organs/tissues?

A

No

49
Q

When can clinical problems arise from normal flora?

A

If they move to a sterile location

50
Q

What can commonly cause harmless bacteraemia?

A

Poor dental hygiene

Dental work

51
Q

What are the second lines of defence in the innate immune system?

A

Phagocyte-microbe interaction
Opsonisation of microbes
Cytokines/chemokines

52
Q

How do phagocytes recognise pathogens using pathogen recognition receptors?

A

Look for pathogen-associated molecular patterns (PAMPs) such as carbohydrates, lipids, proteins and nucleic acids that are not found on self-cells

53
Q

What is the result of opsonins binding to microbial surfaces?

A

Enhanced phagocyte attachment

54
Q

What is the role of cytokines/chemokines as a second line of defence in the innate immune system?

A

Chemoattraction
Phagocyte activation
Inflammation

55
Q

Which are the three main phagocytes?

A

Macrophages
Monocytes
Neutrophils

56
Q

What are the main actions of macrophages?

A

Ingest and destroy microbes
Present microbial antigens to T cells
Produce cytokines/chemokines to stimulate acute phase repsonse

57
Q

What is the action of monocytes?

A

Migrate from blood to infection site where they become macrophages to increase phagocytic ability

58
Q

What type of bacteria do neutrophils ingest and destroy?

A

Pyogenic (staph aureus, strep pyogenes)

59
Q

What are the key cells of the innate immune system except the main phagocytes?

A

Basophils/mast cells
Eosinophils
NK cells
Dendritic cells

60
Q

What is the function of basophils/mast cells?

A

Vasomodulation - early actors of inflammation

61
Q

What is the function of eosinophils?

A

Receptors for IgE to defend against multicellular parasites

62
Q

What is the role of natural killer cells?

A

Kill all abnormal host cells - virus infected/malignant

63
Q

What forms the cellular bridge between the innate and adaptive immune systems?

A

Dendritic cells

64
Q

What must happen to encapsulated bacteria with a large LPS capsule for them to be cleared?

A

Opsonisation

65
Q

What common function do acute phase proteins, complement proteins and antibodies have?

A

Act as opsonins

66
Q

Which acute phase proteins can act as opsonins?

A

CRP

Mannose binding lectin

67
Q

Where are CRP and mannose binding lectin produced?

A

Liver

68
Q

Which complement proteins act as opsonins?

A

C3b

C4b

69
Q

What type of opsonin is not produced in asplenic or hyposplenic pts?

A

Antibodies (IgG, IgM)

70
Q

Give three examples of encapsulated bacteria with large LPS capsules.

A

Neisseria meningitidis
Strep pneumoniae
Haemophilus influenzae b

71
Q

What are the 7 stages of phagocytosis?

A
Chemotaxis and adherence
Ingestion
Phagosome formation
Phagolysosome formation
Enzymatic digestion
Residual body formation
Waste discharge
72
Q

Which method of phagocyte intracellular killing is the most efficient?

A

Oxygen dependent

73
Q

What happens in the oxygen dependent phagocyte intracellular killing mechanism?

A

Respiratory burst releasing hydrogen peroxide, hydroxyl radical, nitric oxide, singlet oxygen, hypohalite

74
Q

What components form the oxygen independent phagocyte intracellular killing mechanism?

A

Lysozyme
Lactoferrin/transferrin
Cationic proteins
Proteolytic and hydrolytic enzymes

75
Q

What is the complement system?

A

20 serum proteins which act in 2 activating pathways

76
Q

What action do C5-9 have in the complement system?

A

Kill pathogens via membrane attack complex

77
Q

What function do C3a and C5a have in the complement system?

A

Phagocyte recruitment

78
Q

What initiates the alternative pathway in the complement system?

A

Cell surface microbial constituents e.g. LPS

79
Q

What activates the mannose binding lectin (MBL) pathway?

A

MBL protein binds to mannose containing residues of proteins found on Salmonella sp. and Candida albicans

80
Q

What brings about a systemic call for help upon infection?

A

Macrophage-derived TNF-alpha, IL-1, IL-6

81
Q

What are the systemic responses to the antimicrobial actions of macrophages?

A

Liver –> CRP and MBL production
Bone marrow –> mobilise neutrophils
Hypothalamus –> increase body temperature
Inflammatory action

82
Q

What inflammatory actions are brought about by TNF-alpha, IL-1 and IL-6?

A

Vasodilation
Increased vascular permeability
Increased adhesion molecules to attract neutrophils

83
Q

What is the effect of of raising body temperature in responding to infection?

A

Increase immune system function

Decrease pathogen function

84
Q

When does sepsis and multi-organ failure occur in infection?

A

Overreaction of TLR4 (pathogen recognition receptor) and complement to microbial toxins causing excessive systemic inflammatory response

85
Q

What happens in excessive systemic inflammatory response?

A

Coagulopathy
Cytokine shower
Vasodilation
Capillary leak

86
Q

What three states can cause a decrease in phagocytosis?

A

Asplenic/hyposplenic pts
Decreased neutrophil number
Deceased neutrophil function

87
Q

What can cause a decreased neutrophil number, leading to neutropenic sepsis?

A

Chemotherapy
Phenytoin
Leukaemia
Lymphoma

88
Q

What can cause decreased neutrophil function?

A

Chronic granulomatous disease

Chediak-Higashi syndrome

89
Q

What is absent in chronic granulomatous disease which prevents effective infection clearance?

A

Respiratory burst

90
Q

What does not form in Chediak-Higashi syndrome which prevents effective infection clearance?

A

Phagolysosomes

91
Q

What is the purpose of local inflammation in response to infection?

A

Creates best environment to contain and deal with infection

92
Q

Which organ is the only one which can deal with blood-borne pathogens?

A

Spleen

93
Q

Is the spleen usually palpable?

A

No

94
Q

What will be palpable upon splenomegaly?

A

Notches on superior border

95
Q

What forms the weak capsule surrounding the spleen which wonders protection but allows expansion?

A

Fibroelastic

96
Q

Which two ligaments hold the spleen in position?

A

Gastrosplenic

Splenorenal

97
Q

What runs within the splenorenal ligament?

A

Splenic artery

98
Q

What is the arterial supply to the spleen?

A

Coeliac trunk –> splenic artery –> 5 vessels –> vascular segments

99
Q

What is the venous drainage of the spleen?

A

Splenic vein and SMV converge to drain into the portal vein

100
Q

How does the spleen filter blood?

A

If aged/abnormal RBCs cannot squeeze through slits between endothelial cells that line the splenic sinuses they are removed

101
Q

What are the two functions of the spleen?

A

Filter and lymphoid organ

102
Q

What is the function of white pulp in the spleen?

A

Mediate antibody responses to capsular polysaccharides of bacteria

103
Q

What forms the marginal zone in the white pulp of the spleen?

A

Interface between follicles and red pulp

104
Q

What is found in the marginal zones of the white pulp of the spleen?

A

Specialised B cells for IgM

105
Q

How does the cordal environment in the red pulp of the spleen allow for phagocytosis and recycling of decreased functioning RBCs?

A

Hypoxic and mechanically challenging

106
Q

What is the difference between the ‘closed’ and ‘open’ circulatory pathways in the red pulp of the spleen?

A

Closed: intact endothelium, rapid transmit
Open: discontinuous endothelium, slower rate of percolation

107
Q

Describe the path of blood flow in the spleen.

A

Splenic arterial blood –> white pulp –> red pulp sinusoids

108
Q

What do cordal macrophages in the red pulp of the spleen do to RBCs they come into contact with?

A

Remove intracytoplasmic inclusions

Remove excess surface membrane

109
Q

What is the overall function of the red pulp of the spleen?

A

Maintain healthy RBC and platelet levels in case of severe bleeding