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Flashcards in Infection Session 3 Deck (109):
1

How is Neisseria meningitidis transmitted?

Direct contact w/respiratory secretions

2

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

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

3

What causes a purpuric rash?

Small bleeding vessels near skin surface

4

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

Blanching: red spots disappear when pressure is applied

5

What is Systemic Inflammatory Response Syndrome (SIRS)?

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

6

What is bacteraemia?

Presence of bacteria in the blood +/- clinical features

7

What is septicaemia?

Clinical term for generalised sepsis where the pt is physiologically unwell

8

What is severe sepsis?

SIRS + organ dysfunction/hypoperfusion

9

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

Hypotension
Decreased urine output (measure creatinine and urea)

10

What is sepsis?

Systemic response to infection - SIRS + infection

11

Does the infection in sepsis have to be confirmed?

No, it can be suspected and still qualify

12

What is septic shock?

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

13

What classification forw Neisseria meningitidis fit into?

G-ve diplococci

14

What virulence factors are present in the meningococcus structure?

Lipopolysaccharide endotoxin
Pili
Polysaccharide capsule

15

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

Promote adherence
Prevent phagocytosis
Capsular antigen defines serogroup

16

What happens in the inflammatory cascade?

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

17

What causes circulatory insult in the inflammatory cascade?

Cytokines causing humoral cascades and RES activation

18

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

GF
Macrophages
Platelets

19

How do cytokines promote coagulation?

Initiate production of thrombin and inhibit fibrinolysis

20

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

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

21

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

FBC
U&Es
PCR
Blood sugar
CRP
Clotting studies
ABG

22

What are the steps in Sepsis 6?

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

23

When should Sepsis 6 be performed?

Within 1 hour of identification of sepsis

24

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

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

25

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

Pressure changes would result in coning --> death

26

How is a diagnosis of bacterial meningitis confirmed?

PCR and culture of blood and CSF (if safe)

27

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

Glucose
Protein
Turbidity
Colour
WBCs
RBCs
Gram stain

28

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

Most likely causative agent for relevant age group
Can it penetrate CSF?

29

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

Acute metabolic derangement

30

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

Notify local Health Protection Unit
Offer prophylactic Abx to pt contacts immediately

31

Generally how does viral meningitis differ from bacterial?

Viral is more common but less severe

32

What is the immune system?

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

33

When are threatening self-cells pathogenic?

Autoimmune disease

34

Define infectious disease.

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

35

How does the immune system recognise pathogens?

Cell surface receptors on innate and adaptive immune cells
Soluble receptors in complement

36

Why must the immune system regulate itself?

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

37

What are the four roles of the immune system?

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

38

Compare and contrast innate and adaptive immunity.

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

39

Which immune response allows for human survival?

Adaptive

40

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

Skin
Mucous membranes
Bronchial cilia

41

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

Diarrhoea
Vomiting
Coughing
Sneezing

42

Are physiological barriers to infection unique to infection?

No, seen in allergy too

43

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

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

44

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

Beta-defensins

45

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

Compete for attachment sites and resources
Produce antimicrobial chemicals

46

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

Non-pathogenic microbes at strategic locations

47

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

K, B12 and other B vitamins

48

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

No

49

When can clinical problems arise from normal flora?

If they move to a sterile location

50

What can commonly cause harmless bacteraemia?

Poor dental hygiene
Dental work

51

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

Phagocyte-microbe interaction
Opsonisation of microbes
Cytokines/chemokines

52

How do phagocytes recognise pathogens using pathogen recognition receptors?

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

53

What is the result of opsonins binding to microbial surfaces?

Enhanced phagocyte attachment

54

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

Chemoattraction
Phagocyte activation
Inflammation

55

Which are the three main phagocytes?

Macrophages
Monocytes
Neutrophils

56

What are the main actions of macrophages?

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

57

What is the action of monocytes?

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

58

What type of bacteria do neutrophils ingest and destroy?

Pyogenic (staph aureus, strep pyogenes)

59

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

Basophils/mast cells
Eosinophils
NK cells
Dendritic cells

60

What is the function of basophils/mast cells?

Vasomodulation - early actors of inflammation

61

What is the function of eosinophils?

Receptors for IgE to defend against multicellular parasites

62

What is the role of natural killer cells?

Kill all abnormal host cells - virus infected/malignant

63

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

Dendritic cells

64

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

Opsonisation

65

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

Act as opsonins

66

Which acute phase proteins can act as opsonins?

CRP
Mannose binding lectin

67

Where are CRP and mannose binding lectin produced?

Liver

68

Which complement proteins act as opsonins?

C3b
C4b

69

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

Antibodies (IgG, IgM)

70

Give three examples of encapsulated bacteria with large LPS capsules.

Neisseria meningitidis
Strep pneumoniae
Haemophilus influenzae b

71

What are the 7 stages of phagocytosis?

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

72

Which method of phagocyte intracellular killing is the most efficient?

Oxygen dependent

73

What happens in the oxygen dependent phagocyte intracellular killing mechanism?

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

74

What components form the oxygen independent phagocyte intracellular killing mechanism?

Lysozyme
Lactoferrin/transferrin
Cationic proteins
Proteolytic and hydrolytic enzymes

75

What is the complement system?

20 serum proteins which act in 2 activating pathways

76

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

Kill pathogens via membrane attack complex

77

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

Phagocyte recruitment

78

What initiates the alternative pathway in the complement system?

Cell surface microbial constituents e.g. LPS

79

What activates the mannose binding lectin (MBL) pathway?

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

80

What brings about a systemic call for help upon infection?

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

81

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

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

82

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

Vasodilation
Increased vascular permeability
Increased adhesion molecules to attract neutrophils

83

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

Increase immune system function
Decrease pathogen function

84

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

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

85

What happens in excessive systemic inflammatory response?

Coagulopathy
Cytokine shower
Vasodilation
Capillary leak

86

What three states can cause a decrease in phagocytosis?

Asplenic/hyposplenic pts
Decreased neutrophil number
Deceased neutrophil function

87

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

Chemotherapy
Phenytoin
Leukaemia
Lymphoma

88

What can cause decreased neutrophil function?

Chronic granulomatous disease
Chediak-Higashi syndrome

89

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

Respiratory burst

90

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

Phagolysosomes

91

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

Creates best environment to contain and deal with infection

92

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

Spleen

93

Is the spleen usually palpable?

No

94

What will be palpable upon splenomegaly?

Notches on superior border

95

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

Fibroelastic

96

Which two ligaments hold the spleen in position?

Gastrosplenic
Splenorenal

97

What runs within the splenorenal ligament?

Splenic artery

98

What is the arterial supply to the spleen?

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

99

What is the venous drainage of the spleen?

Splenic vein and SMV converge to drain into the portal vein

100

How does the spleen filter blood?

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

101

What are the two functions of the spleen?

Filter and lymphoid organ

102

What is the function of white pulp in the spleen?

Mediate antibody responses to capsular polysaccharides of bacteria

103

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

Interface between follicles and red pulp

104

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

Specialised B cells for IgM

105

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

Hypoxic and mechanically challenging

106

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

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

107

Describe the path of blood flow in the spleen.

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

108

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

Remove intracytoplasmic inclusions
Remove excess surface membrane

109

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

Maintain healthy RBC and platelet levels in case of severe bleeding