Sepsis and Innate Immunity Flashcards
Define sepsis
Life threatening organ dysfunction due to a dysregulated host response to infection
Define septic shock
Persisting hypotension requiring treatment to maintain blood pressure despite fluid resuscitation already being given
Define bacteriaemia
The presence of bacteria in the blood
Not multiplying
No symptoms
What does the early warning score for sepsis look for?
Increased resp rate
Increased heart rate
Very low or high temperature
Low blood pressure
What is included in the sepsis six bundle?
Give high flow oxygen Give IV fluids Give empirical IV antibiotics Take blood for cultures Take blood for lactate Check the urine output
Apart from the sepsis six bundle, what other investigations should you order?
FBC U&E EDTA bottle for PCR Blood sugar LFTs CRP Coagulation studies Blood gases Other microbiology samples (CSF, urine)
What is the most likely organism causing meningitis?
Neisseria meningitidis
How is meningitis spread?
Direct contact with respiratory secretions
What are the local effects of cytokines?
Promote wound repair
Recruit the reticuloendothelial system
What are the systemic effects of cytokines?
Stimulating growth factor, macrophages and platelets to control infection
How can cytokines in sepsis lead to organ ischaemia?
Initiate production of thrombin
Promote coagulation
Cytokines also inhibit fibrinolysis
Microvascular thrombosis
Describe the management for sepsis
Sepsis six bundle
Consider early referral to ITU
Regular monitoring and reassessment
What antibiotic do we use to treat meningitis?
Ceftriaxone
Describe neisseria meningitidis
Gram negative diplococcus Numerous types - B is most common in UK Type based on capsular antigen Up to 25% young adults are carriers Spread by aerosols and nasal secretions
What types of meningitis are covered in the multiple vaccine?
ACWY
Define infectivity
Capacity of microorganism to establish itself within the host
Define virulence
Capacity of the pathogen to harm the host
What is the immune system?
All the cell and organs that contribute to the immune defences against infectious and non-infectious conditions
Distinguishing between self and non-self
Define an infectious disease
When the pathogen succeeds in evading and/or overwhelming the host’s immune defences
What are the roles of the immune system?
Pathogen recognition
Containing/eliminating the infection
Regulating itself
Remembering pathogens
Name the 4 types of barriers that are the first line of defence
Physical
Physiological
Chemical
Biological
Describe the physical barriers of defence
Skin (epidermis has no vessels so cannot spread that way)
Mucous membranes - active and dynamics, secrete antimicrobials, cilia
Describe some physiological barriers against infection
Diarrhoea
Vomiting
Coughing
Sneezing
Describe the chemical barriers against infection
Low pH of the skin, stomach and vagina - Bacteria are extremely sensitive to acidic environments
Antimicrobial molecules: IgA (tears, salvia), Lysozyme (perspiration, urine, sebum), mucus, beta-defensins (epithelium), gastric acid
Describe the benefits of normal flora
Compete with pathogens for attachment sites and resources
Produce antimicrobials
Synthesis vitamins (K, B12 and other B vitamins)
Give some examples of normal flora of the skin
Staph aureus Staph epidermidis Strep pyogenes Candida albicans Clostridium perfringens
Give some examples of normal nasopharyngeal flora
Strep pneumoniae
Neisseria meningitidis
Haemophilus species
List some patients who are high risk when present with bacteriaemia
Asplenic/hyposplenic
Damaged/prosthetic valves
Previous infective endocarditis
What pathologies can lead to overgrowth of normal flora?
Diabetes
AIDS
Malignancy
Chemotherapy
What are the 3 main phagocytes?
Macrophages
Monocytes
Neutrophils
Describe the features of macrophages
Present in all organs
Ingest and destroy microbes
Present antigens to T cells
Produce cytokines/chemokines
Describe the features of monocytes
Present in blood
Recruited at infection site and differentiate into macrophages
Describe the features of neutrophils
Present in the blood
Increased during infections
Recruited by cytokines to site of infection
Ingest and destroy microbes
What are PAMPs?
Pathogen-associated molecular patterns
Present on the microbe
What the phagocytes use to recognise it
Can be carbohydrate, lipid, protein or nucleic acid
Define opsonisation
Coating proteins called opsonins that bind to microbial surfaces leading to enhanced attachment of phagocytes and clearance of microbes
Give some examples of opsonins
Component - C3b, C4b
Antibodies - IgM, IgG
Acute phase proteins - CRP, MBL
Encapsulated bacteria cannot be cleared unless …
Opsonised
Give examples of some encapsulated bacteria
Neisseria menigitidis
Strep pneumoniae
Haemophilus influenzae B
What are the steps of phagocytosis?
Chemotaxis and adherence to microbe Ingestion Formation of phagosome Fusion with lysosome Digested on microbe by enzymes Formation of residual body containing indigestible material Discharge of waste material
What are the 2 types of phagocyte killing mechanisms?
Oxygen dependent (respiratory burst) Oxygen independent
What factors contribute to the oxygen independent killing mechanism?
Lysozyme
Lactoferrin/transferrin
Cationic proteins
Proteolytic and hydrolytic enzymes
How may complement proteins are there?
20
Describe the 2 complement activating pathways
Alternative - initiated by cell surface microbial constituents
MBL - initiated when MBL binds to mannose containing residues of proteins found on many microbes
Which complement proteins recruit phagocytes?
C3a and C5a
Which complement proteins contribute to the membrane attack complex?
C5-C9
What are the actions of TNF-alpha, IL-1 and IL-6?
CRP and MBL released Neutrophil mobilisation Vasodilation Vascular permeability Adhesion molecules attract neutrophils Increase body temperature
Why are asplenic people susceptible to encapsulated bacteria?
They have reduced phagocytosis
The spleen normally contains many macrophages
How can e-coli be caught?
Eating contaminated food Touching infected animals Contact with people who have the illness Drinking inadequately treated water Swimming/playing in contaminated water
Main symptoms of E-coli infection:
Diarrhoea
Fever
Stomach cramps
(Can last up to 2 weeks)
Describe a few basic features of E-coli
Gram negative
Rod-shaped
Anaerobic
Describe a few basic features of strep pneumoniae
Gram positive Anaerobic Present in many healthy carriers Main cause of CAQ pneumonia Transmission: sneezing, coughing, direct contact Encapsulated
