What is sepsis?
Sepsis is a life threatening organ dysfunction due to a dysregulated host response to infection.
Septic shock is persisting hypotension requiring treatment to maintain blood pressure despite fluid resuscitation.
What are the symptoms of sepsis?
- Respiratory rate higher than 25 breaths/min
- Need for oxygen to keep O2 saturation above 91%
- Systolic BP is less than 91mmHg
- Heart rate is greater than 130 bpm
- No urine output for over 18hrs
- Responds only to voice or pain (otherwise unresponsive)
- Non blanching rash - mottled skin or ashen looking and cyanotic
- Neutropenia or chemotherapy within the last 6 weeks
What are possible complications of sepsis?
- Irreversible hypotension
- Respiratory failure
- Acute kidney injury and renal failure
- Raised intracranial pressure
- Ischaemic necrosis of the extremities
What possible infections can cause sepsis?
All infections could cause sepsis, but here are some to be more specific:
- abdominal infections
- wound infection
- device related infection
What investigations would you take to diagnose sepsis and the underlying infection?
- Blood culture
- PCR of blood culture bacteria
- Lumbar puncture (if it is safe)
- Microscopy and culture of CSF
- PCR of CSF
- Microscopy and culture of CSF
- PCR of CSF
Describe the helpful mnemonic for sepsis
Extreme shivering/ muscle pain
Passing no urine
I feel like I might die.
Skin mottled or discoloured
What is the sepsis 6 bundle?
Actions that should be completed in 1 hour after the diagnosis of sepsis.
- Give high flow oxygen
- Take blood cultures
- Give IV antibiotics
- Give a fluid challenge
- Measure lactate
- Measure urine output
What supportive care would you give to someone with sepsis?
- Referral to the ITU
- Utilise the sepsis 6 bundle
- Montior the patient with regular reassessments
What specific treatment would you give to someone with sepsis?
- Use an agent that is likely to be active against the pathogens that have caused the primary infection
- The agent should be able to get to the site of infection
Describe in brief, the layout of the immune response
Pathogen recognition: receptors on the cell surface
Containing and eliminating the infection: killing and clearance mechanisms
Regulating itself: minimum damage to the host
Remembering pathogens: preventing the disease from recurring
What are the two forms of immunity and what do they do?
Innate immunity: provides a broad and immediate response.
Adaptive immunity: follows innate immunity and is more specific, providing long lasting protection.
What are the two lines of defence in innate immunity?
First line of defence: innate barriers
Second line of defence: phagocytes and chemicals that help in the inflammatory response
What are the innate barriers we have against infections?
- Physical Barriers
- Physiological barriers
- Chemical barriers
- Biological barriers
Explain and give examples of physical barriers in innate immunity
Physical Barriers - actually physically blocking the infection from entering the body
Examples: Skin, mucous membranes, bronchiole cillia
Explain and give examples of physiological barriers in innate immunity
Physiological Barriers - barriers that intend to expel the pathogen from the body
Examples: vomiting, diarrhea, sneezing, coughing
Explain and give examples of chemical barriers in innate immunity
Chemical Barriers - intend to kill the pathogens before it can enter the body
Examples: low pH found on the skin, in stomach acid, and in the vagina
Antimicrobials found in tears, lysozymes, mucus, gastric acid
Explain and give examples of biological barriers in innate immunity
Biological Barriers - non pathogenic microbials present on specific and advantageous surfaces
Examples: E. coli in the gut, Staphylococcus aureus on the skin, and Neisseria meningitidis in the nasopharynx
Briefly outline the second line of defence in the innate immune response
Phagocytes get involved in attempting to destroy the pathogen.
Phagocytes are signalled to where the microbes are and will attack them.
What phagocytic cells are involved in the innate immune response?
- Basophils/Mast cells
- Natural Killer cells
- Dendritic cells
What do macrophages do in the innate immune response?
- Present in all organs
- Ingest and destroy microbes through phagocytosis
- are APC (present antigens to T cells in adaptive immunity)
- Produce cytokines and chemokines
What do monocytes do in the innate immune response?
- Present in the blood
- Recruited at the site of infection where they then differentiate into macrophages
What do neutrophils do in the innate immune response?
- Present in the blood and increase in numbers during infection
- Led by chemokines to the site of infection
- Ingest and destroy pyogenic bacteria (Staph. aureus, and Strep. pyrogenes)
What do basophils do in the innate immune response?
- Are one of the early actors in inflammation through vasomodulation
- Also important in allergy responses
What do eosinophils do in the innate immune response?
- Provide defence against mutli cellular parasites (worms)
What do natural killer cell do in the innate immune response?
- Kill all abnormal host cells (either virus infected or malignant)
What do dendritic cells do in the innate immune response?
- Antigen presenting cells to the T cells
What are the two mechanisms that allow phagocytes to target microbes?
PAMPs and PRRs
Opsonin proteins and Opsonin receptors
What do PAMPs do?
PAMPs are pathogen-associated molecular patterns that sit on the surface of the microbial.
They are recognised by the relevant phagocytic structures, PRRs, pathogen recognition receptors.
This allows phagocytes to act and target the pathogens.
What do opsonins do?
Similar to PAMPs, but requires the pathogen to be opsonised first.
Pathogens are opsonised by the binding of IgG molecules or Cb3 molecules to their surface.
Phagocytes have receptors that recognise IgG and Cb3, when they detect these molecules it signals to the phagocyte to engulf and destroy the microbe.
Outline the process of oxygen dependent phagocytosis