Infection S3 (Done) Flashcards
What are the clinical features of someone presenting as an emergency case with suspected severe infection?
Sudden onset
High temp (>38) and chills (Fever)
Tachycardic and hypotensive
High resp rate
Headache
Nausea
Weakness and generalised muscle pain
Abdominal pain
Photophobia
Pale, cool extremities
What is SIRS?
Give a defintion, why it occurs and the clinical criteria
Systemic inflammatory response syndrome
Response to non-specific insult (Ischaemia, trauma, infection)
Clinical criteria = two or more of:
Temperature = <36 or >38
HR = >90bpm
RR = 20/min or pCO2 of <4.3kPa
WBC = <4x10^9/L or >12x10^9/L
Give the definition of bacteraemia
Presence of bacteria in blood (+/- clinical features)
Define sepsis
Define septicaemia
Sepsis:
Systemic response to infection defined as:
SIRS + documented or presumed infection
Septicaemia:
Generalised sepsis
Define severe sepsis
SIRS
+
Organ dysfunction/hypoperfusion
How can we assess if bodily organs are hypo-perfused
Hypotension, decreased urine output
Define Septic shock
Severe sepsis
+
Persistent hypotension despite IV fluid administration
Label the white boxes with name of stucture and function regarding infection
Black boxes an be labelled with structure only
White, top left to bottom:
Lipopolysaccharide - Endotoxin, triggers inflammation
Pilus - Enhances attachment
Polysaccharide capsule - Promtes adherance, prevents phagocytosis
Black, top to bottom:
Outer membrane
Inner membrane
Give the inflammation cascade that occurs after endotoxins bind to macrophages
Asume homeostasis cannot be restored
Local:
Cytokines (TNF and ILs)
Stimulates inflammatory response to promote wound repair and recruit the reticuloendothelial system
Systemic:
Cytokines released into circulation
Stimulates growth factor, macrophages and platelets
Goal is homeostasis restoration
SIRS:
Homeostasis not restored
Cytokines activate humoral cascades and RE system leading to ciculatory insult/damage
Describe how sepsis can lead to microvascular insult/damage
Cytokines promote production of thrombin therfore coagulation
Cytokines also inhibit fibrinolysis
Coagulation cascade leads to microvascular thrombosis
Can lead to organ ischaemia, dysfunction and failure
Microvascular injury is the major cause of shock and multiorgan failure
What investigations might you perform for someone with suspected infection/sepsis?
FBC
Urea and electrolytes
Blood sugar
Liver function tests
CRP testing
Clotting studies
Blood gases
EDTA for PCR
What is the ‘sepsis six’?
6 actions to be performed within an hour of a patient going septic or a patient coming in in suspected sepsis
As follows:
High flow oxygen administration
Take blood cultures + other cultures, consider source control
Administer empirical IV antibiotics
Measure serum lactate
Start IV fluid resuscitation
Commence accurate urine output measurement
What are some specific features of a patient with Nesseria menigitidis infection?
Non blanching (purpuric) rash
Neck stiffness
What is the most common cause of meningitis?
Bacterial
Nesseria menigitidis
How is Nesseria meningitidis spread?
Direct contanct with infected respiratory secretions (droplets, aerosols)
Is Nesseria meningitidis normally pathogenic?
No, in most it is a harmless commensal bacteria
In the unlucky few it is pathogenic
What antibiotic is best suited for treatment of bacterial meningitis and why?
Ceftriaxone:
Penetrates CSF
Active against Nesseria meningitidis
Give some of the serious complications of severe infection/meningitis
Irreversible hypotension
Resp failure
AKI (renal failure)
Raised intercranial pressure
Ischaemic necrosis of hands and feet
What tests are required for confirmation of bacterial meningitis infection
Blood culture
PCR of blood
Lumbar puncture (if safe) - Culture and PCR of CSF
What examinations can be carried out on CSF?
Glucose and protein estimation
M,C&S:
Appearance - Normal, cloudy, blood stained
WBC and RBC count
Gram staining
PCR
What conditions can cause the CSF to appear normal, cloudy/turbid or blood stained?
Normal:
Normal conditions, Viral meningitis
Cloudy/Turbid:
Bacterial meningitis, Tuberculous meningitis
Blood-stained:
Sub-Arachnoid haemorrhage
Give some details on the structure and variation of Nesseria meningitidis
Gram negative diplococcus
Polysaccharide capsular antigen (prevents phagocytosis)
Outer membrane acts as an endotoxin
Numerous Serogroups (A, B, C, W-135)
Of the different serogroups of Nesseria meningitidis which is most prevalent
- In UK
- Worldwide
UK:
B
Worldwide:
A
Describe the prevention of meningitis
Vaccination:
N. meningitidis C vaccine available
ACWY vaccines used for immunocompromised patients and travel protection
B vaccine not routine
Prophylaxis:
Notifiable disease
Report cases to local health protection unit
Close contacts can be given antibiotic prophylaxis and considered for vaccination
What are the major factors contributing to the outcome of the host-pathogen relationship?
Virulence
Number of organisms
Host’s immune response
Define Immune system
Cells and organs that contribute to immune defences against infectious and non-infectious conditions
Define infectious disease
When the pathogen succeeds in invading and/or overwhelming the host’s immune defenses
What are the key roles of the immune system?
Give a very brief description of each
Pathogen recognition:
Cell surface and soluble receptors
Containing/eliminating the infection:
Killing and clearance mechanisms
Regulating itself:
Causing minimum damage to host (resolution)
Remembering pathogens:
Preventing re-occurence
What are the key features of innate immune response?
Fast (within seconds)
Recognises groups of pathogens
Lack of memory
No change in intensity w/repeat exposure
What are the key features of the adaptive immune system?
Slow (3-4 days)
Response specific to one pathogen
Immunologic memory
Variable intensity (increases with repeat exposure)
What are the first lines of defense in the innate immune system?
What is their overall function?
Barriers:
Physical barriers
Physiological barriers
Chemical barriers
Biological barriers
Function:
Factors that limit entry and growth of pathogens
Give examples of physical barriers of the innate immune system
Their collective immune function?
Skin
Mucous membranes
Bronchial cilia
Function:
Prevent ingress of pathogens
Give examples of physiological barriers of the innate immune systems
What is their collective function?
Diarrhoea
Vomiting
Coughing
Sneezing
Function:
Mechanical ejection of pathogen/irritant
What are the chemical barriers of the innate immune system?
Give functions of each factor
Low pH:
Skin (5.5)
Stomach (1-3)
Vagina (4.4)
Number of pthogens sensitive to low pH
Antimicrobial molecules:
IgA - Prevents microorganism binding (tears, saliva)
Lysozyme (sebum, perspiration, urine)
Mucous - Traps pathogen
B-Defensins - Antiviral (epithelium)
Gastric acid + Pepsin
What is the main biological barrier of the innate immune system?
Functions?
Commensal microbes:
Nasopharynx
Mouth/throat
Skin
GI tract
Vagina (lactobacillus)
Absent in internal organs (where they would cause disease)
Functions:
Compete with pathogens for attachment sites and resources
Produce antimicrobial chemicals
Synthesise Vit K, B12 and other B vitamins
Give some skin and nasopharynx commensal species
Skin:
Staph aureus + Staph epidermidis
Strep pyogenes
Candica albicans
Clostridum perfringens
Nasopharynx:
Strep Pneumoniae
Nesseria meningitidis
Haemophilus spp
In what situations do clinical problems arise regarding commensal displacement?
When normal flora is displaced
Breaching skin:
Skin loss (burns)
Surgery
IV drug use (endocarditis)
IV lines
Faeco-oral
Fecal-perineal-urethral route:
UTI
Poor dental hygiene/dental work:
Dental extraction
Gingivitis
Flossing
Describe the clinical concequences of poor dental hygiene/dental work
Common cause of harmless bacteraemia
Serious infection risk:
Hypo or asplenic patients
Damaged or prosthetic heart valves
Previous infective endocarditis
Serious consequences:
Infective endocarditis
What are the causes and clinical consequences of decrease or increase in normal flora?
Normal flora overgrowth can occur in immunocompromised patients:
Can be caused by:
Diabetes
AIDS
Malignancy
Chemotherapy
Normal flora depleted by antibiotics:
Allows pathogens to grow
Can cause:
Severe colitis (Clostridium difficile)
Thrush (Candica albicans)
What are the second line innate barriers of the immune system?
What is their collective function?
Phagocytes
Chemicals
Inflammation
Function:
Contain and clear infection
What is the main function of phagocytes?
Recognition and killing (phagocytosis etc) of microbes
What are the phagocytic cells of the innate immune system?
Macrophages
Monocytes
Neutrophils
What is the immune function of macrophages?
Present in all organs
Ingest and destroy microbes (phagocytosis)
Present microbial antigens to T cells
Produce cytokines/chemokines (chemoattractants)
What is the immune function of monocytes?
Present in blood
Recruited to infection site to differentiate to macrophages
What is the immune function of neutrophils?
Presnt in blood
Increased during infection
Recruited by chemokines (chemoattractants) to site of infection
Ingest and destroy pyogenic bacteria (E.g. Staph aureus and Strep pyogenes)
What are the non-phagocytic cells of the innate immune system?
Basophils / Mast cells
Eosinophils
Natural killer cells
Dendritic cells
What are the functions of Basophils / Mast cells?
Early actors of inflammation
Vasomodulation
Important to allergic response
What is the function of Eosinophils?
Defense against multicellular parasites (worms)
Release IgE (binds to parasite)
What is the function of Natural killer cells?
Kill all abnormal host cells (malignant or virally infected)
What is the innate immune function of the dendritic cells
Present microbial antigens to T cells
The messengers between innate immune system and adaptive
How does the innate immune system recognise pathogens?
PAMPS:
Pathogen-associated molecular patterns
Membrane structures of the pathogen that can be recognised
Can be proteins, nucleaic acids, carbohydrates, lipids etc
Thse are recognised by Pathogen recognition receptors (PRRs) which bind
Opsonins:
Opsonins coat microbial surfaces leading to enhances attachment of phagocytes and clearance of microbe
Less specific than PAMPS-PRR
Give some examples of different PAMPS and their PRR
Gram negative bacteria:
Lipopolysaccharide - TLR4
Lipoproteins and lipopeptides - TLR2
Gram positive bacteria:
Peptidoglycan - TLR2
Lipoteichoic acids - TLR4
Mycobacteria:
Lipoarabinomannan - TLR2
Bacterial flagella:
Flagellin - TLR5
Give examples of Opsonins
Complement proteins:
C3b
C4b
Antibodies:
IgG
IgM
Acute phase proteins:
CRP
Mannose binding lectin
What type of bacteria are opsonins particularly important in clearing?
Give some examples
Encapsulated bacteria
**E.g. **
Nesseria Meningitidis
Strep Pneumoniae
Haemophilus influenzae
Describe the process of phagocytosis
- Chemotaxis and adherence to microbe
- Ingestion of microbe
- Formation of phagosome
- Fusion of phagosome with lysomsome to form phagolysosome
- Digestion
- Formation of residual body
- Discharge of residual body
What are the phagocyte intracellular killing mechanisms?
Oxygen dependent pathway:
Toxic O2 products damage pathogen
E.g. Superoxide, Hydrogen peroxide, Nitric oxide, O-, Hypohalite
Oxygen independent pathways:
Lysozyme
Lactoferrin or transferrin
Cationic proteins (cathepsin)
Proteolytic an hydrolytic enzymes
Describe the complement system
Proteins C1 to C9
Activation:
Alternative pathway
Initiated by cell surface constituents
OR
MBL pathway
Initiated when mannose binding lectin binds to mannose containing residues of proteins found on salmonella spp./Candica albicans
Give the functions of the important complement proteins
C3a and C5a:
Recruitment of phagocytes
C3b - C4b:
Opsonisation of pathogens
C5 - C9:
Killing of pathogens
Membrane attack complex (Forms pore in cell membrane leading to cell lysis)
Apart from the complement system what is the other chemical defense system of the second line innate immune system?
Cytokine/Chemokines
What cytokines/chemokines are produced by the liver and what is their function?
TNF-a, IL-1, IL-6
Functions:
Liver:
CRP and MBL release
Bone Marrow:
Neutrophil mobilisation
Inflammation:
Vasodilation
Vascular permaeability
Adhesions molecules (attract neutrophils)
Hypothalamus:
Increase body temp
How can over-reaction of the innate immune system lead to clinical problems
Infection (E.g. Gram negative bacteria)
Overreaction of the TLR4 receptor and complement lead to overrecruitment of phagocytes and excessive tissue reaction
Excessive systemic inflammatory response
Cytokine shower
Coagulopathy
Vasodilation
Capillary leak
All reduce tissue/organ perfusion
Sepsis and multi-organ failure
Why are hypo or asplenic patients at greater risk of infection?
Spleen hold half the body monocytes
Polysaccharide encapsulted bacteria resist opsonisation by complement proetins
Natural antibodies produced in the spleen required for successful immune response (opsonisation)
Give some conditions that can cause reduced phagocytosis
Decreased spleen function:
Asplenic or hyposplenic patients
Decreased neutrophil number:
Cancer chemotherapy
Other drugs
Leukaemia and lymphoma
Decreased neutrophil function:
Chronic granulomatous disease (no oxidative burst)
Chediak-Higashi syndrome (no phagolysosome formation)
