Define sepsis
Life-threatening organ dysfunction due to a dysregulated host response to infection
Which organisms commonly cause sepsis and why?
Though both gram (+) and (-) can, -ve is more common as it has LPS (e.g e.coli). LPS activates macrophages and NK cells which further amplify the immune response, producing positive feedback
What are the 2 main pathophysiology pathways of sepsis?
Immune system and coagulation
Describe the general overview of what happens once the immune system has been activated
- TLR is activated and triggers a signalling cascade, recruiting adaptor proteins and activating transcription factors with NK kappa beta
- activation of cytokines and mediators can cause a ‘cytokine storm’
- leads to acute inflammation and stimulated adaptive immunity
Describe 3 vascular and 1 cellular change that occurs during inflammation
Vascular: vasodilation, vascular permeability, increased adhesion of WBCs
Cellular: recruitment and activation of neutrophils
What does NF kapa beta do?
Protein complex that controls the transcription of DNA and cytokine production
What happens to the fluid volume and cardiovascular system following sepsis?
Absolute hypovolemia; more fluids going into the tissues to combat infection -> lowers the BP, triggering baroreceptors to initiate compensatory tachycardia
The increased vascular permeability and vasodilation also lowers the TPR/SVR
What happens to the bloodflow to organs and why?
The reduced circulating volume reduces the venous return: so CO falls, BP falls more and the flow reduces to organs.
The activated coagulation pathway is also causing microthrombi to distribute throughout circulation
What happens to the lungs as sepsis progresses?
Due to the difficulty of removing CO2 and circulating inflammatory mediators the patient will have tachypnoea and shortness of breath.
The surfactant dries out which may develop into acute resp distress syndrome
What happens in acute resp distress syndrome?
Fluid leaks from blood vessels into alveoli so they become unstable and collapse - the amount of circulating O2 drops
Why do patients experience sepsis become confused?
Not getting enough oxygen: As the body goes deeper into shock it protects the core and continually decreases supply to the brain
Not getting enough glucose:
Low O2 states increase insulin resistance so glucose cannot access the tissues or the brain.
What happens to the pH in the tissues?
Anaerobic respiration increases so the pH falls, inducing metabolic acidosis
Name 2 things you might see in the blood as a result of sepsis
- Increased blood sugar; Low O2 increases insulin resistance and the body’s stress response (cortisol) promotes gluconeogenesis
- CRP (a marker of inflammation)
Describe the coagulation pathophysiology
Complement C5 splits into C5a and C5b. C5b activates MAC and C5a increases expression of TF on the surface of monocytes - initiating the coagulation cascade
Clots retrigger inflammation ad the immune response - positive feedback
Why does purpura happen? How reliable of a sign is it?
The fibrin deposited in the blood vessels make bloodflow harder and accessive clots deplete the clotting factors and cause bleeding
Purpura is not a key recognition sign as it doesn’t always appear and can appear very late
What acronym helps you recognize sepsis?
TIME: Temperature (higher or lower than normal) Infection Mental decline Extremely ill; severe pain or discomfort
Name 5 red flags of sepsis
- HR >130 bpm
- Resp rate >25 per min
- Not passed urine in last 18 hours
- Lactate >2mmol/L
- acute confusional state
What is SIRS and what criteria define it?
SIRS is present if there are at least 2 of the following present (No longer the primary way to identify sepsis…)
- Temp below 36 or above 38.3
- HR >90
- Abnormal resp rate and pCO2
- Increase in WBC count
- Confusion
- Blood glucose >7mmol/L in non-diabetic patients
What is the SOFA and the qSOFA score?
SOFA: suspected infection plus a change in 2 or more of the criteria involving resp, hematology (platelet count), liver (serum bilirubin), renal (serum creatinine or urine output), brain and cardiovascular (hypotension and vasopressor requirement)
qSOFA is a quick bedside way to assess:
- resp rate of 22/min +
- altered mentation (Glasgow coma scale less than 15)
- systolic BP of 100 mmHg or less
What topics are examined in the NEWs score and how is it scored/used?
POTSRL
Topics score max 3 for each 1. Respiration 2. systolic BP 3. Pulse rate 4. Oxygen saturation (if they require oxygen they score 2) 5. temperature 6. level of consciousness If the NEWS score reaches 5 use clinical judgement
How would you manage sepsis?
Hint: The sepsis 6 bundle
Give…
- IV antibiotics: initially broad to ensure the microorganism will respond
- IV fluids
- O2
Take…
- Lactate levels
- Blood culture; identify the presence of infection
- Urine output measurement
When and why would you give vasopressin?
Within 6 hours if the patient’s hypotension is not responding to the initial fluid rescucitation
What type of antibiotic is doxycycline and how does it work?
Tetracycline
Doxycycline inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit
Name 5 samples you might take in a patient presenting with symptoms alike to sepsis
- Blood cultures – to see if a pathogen can be grown from her blood
- Urea and Electrolytes – to determine her renal function
- Liver Function Tests – determine her liver function
- Coagulation screen (aPPT / PT) – to check clotting
- Blood gas - to estimate Serum Lactate and acid /base balance
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Intro36
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Strep, Staph and pathogens54
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Sepsis26
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Enteric and Diarrhoeal Disease62
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Antimicrobial adaptations20
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Childhood Infections43
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Antimicrobial agents50
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Vaccinations36
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Viral adaptations (7.1)27
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Viruses and Cancer (7.2)33
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Infections of the genital tract47
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HIV34
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Hepatitis72
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Malaria43
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Prions34
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COVID-196
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11.1: Hospital acquired infections50
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11.2: Fundamentals of infection control13
