Pathogens VI- Sepsis

Question 1

1- What happens when there is a localised infection?
2- Compare the basic effect for an intracellular/extracellular infection?
3- How do Pathogenic organisms resist innate immunity?

Answer 1

1- Localised response (NOT SEPSIS)

2-
EX: - More inflammation - Lots of neutrophils
IN: - Limited inflammation - NK cells present - Few neutrophils

3- Virulence factors

Question 2

If controls don’t work for local infections as pathogens resists innate immunity, what is needed?

Answer 2

• More robust response required
  -> To clear pathogen
  NOT SEPSIS

Question 3

What symptoms arise due to local infections?

Answer 3

Question 4

What can a suppressed immune system lead to? (5)

Answer 4

1- Neutropaenia: Neutropaenic sepsis

2- Better environment for organisms: Mucus layer in COPD/CF + Glucose secretion in diabetes

3- Hypo-responsive immunity - Measles virus suppression of TH1 responses

4- Reactivation of dormant organisms
- Latent TB infection
- Shingles

5- Access to deeper tissues
- Ventilator-associated pneumonia
- Catheter-associated UTI

Question 5

Which organisms take advantage of a weakened immune system?(4)

Answer 5

Staphylococcus epidermidis,
Pseudomonas aeruginosa,
Viridans group streptococci,
Klebsiella pneumoniae

Question 6

1- Symptoms and signs of infection are a product of what? What does this mean?

2- Relate this to what would happen with a weakened immune system.

Answer 6

• Inflammatory response > So limited immune response will produce less of these symptoms
  ->Neutropaenic sepsis

2- Weakened immune system = less of an inflammatory response = produce less symptoms, no matter how bad the infection is.
> Someone = seriously ill but not show the signs

Question 7

What happens when the infectious agent reaches the bloodstream?

(What do PBMCs do?)

Answer 7

• Infection cannot be contained at the primary site and begins to spread, often to the bloodstream. > SYSTEMIC INFLAMMATORY RESPONSE SYNDROME =

Activation of peripheral blood mononuclear cells (monocytes) + Large amount of pro-inflammatory immune products at the primary site leads to systemic signs of infection.
- Fever
- HR
- CRP level raised
- WCC raised

Question 8

When does Systemic inflammatory response syndrome SIRS become Sepsis?

Answer 8

• SIRS response to infection begins to lead to non-perfusion of organs (by vasodilatation associated with severe non-localised oedema, reduced blood pressure and hyper- coagulation) and then these begin to fail.
  > So, sepsis is linked to organ failure (and vice-versa)

Question 9

What do You need to remember when it comes to sepsis ans SIRS?

Answer 9

• Aren’t “diseases” > manifestations of a primary condition that is not being controlled > look for the underlying cause!
  e.g. Sepsis secondary to cellulitis manage 2g IV flucoxacillin

Question 10

PBMC-derived TNFα results a feedback-loop of…

Answer 10

• Tissue-factor expression, neutrophil activation and NO production

Question 11

How can sepsis lead to septic shock?

Answer 11

• Spread of pro-inflammatory material is incredibly high and oxygen demand by tissues is excessive, it can lead to decompensation(failure of multiple organ systems)
  > Sepsis gets so severe that your body’s response to infection starts harming you more than the infection itself.

Question 12

In septic shock Low BP/MAP is compensated by what?

Answer 12

• Constriction of blood vessels and increased heart rate/force-of-contraction

Question 13

Poor perfusion of organs and loss of central blood-pressure regulation are severe what happens if ongoing severe immune responses continue?

Answer 13

• Depletion of a patients WBCs/ proteins/ molecules and activation of anti-inflammatory mechanisms
• As immune response is causing patients symptoms depletion of immune cells alleviates the symptoms from the immune response, even though the patient is still very ill.
  COMPENSATORY ANTI-INFLAMMATORY RESPONSE SYNDROME

Question 14

How can sepsis lead to compensatory anti inflammatory response syndrome?

Answer 14

Question 15

What does sepsis often result from? What primary condition?

Answer 15

• Pulmonary infection (but can be anywhere)

Question 16

What bacteria is Sepsis most commonly caused by?

Answer 16

• Escherichia Coli

Question 17

SEPSIS Acronym

Answer 17

Question 18

Define terms often confused with sepsis:
1- Septicaemia
2- Bacteraemia

Answer 18

1- Blood poisoning
2- Detectable presence of bacteria in blood stream

Question 19

What is the criteria to be diagnosed with SIRS?

Answer 19

• SIRS = A body-wide response involving inflammatory mediators – not always caused by infection

> SIRS defined as two or more these in the same patient

Question 20

DEFINE:
- Sepsis
- Septic shock
- Comensatory anti-inflammatory response syndrome (CARS)

Answer 20

• Sepsis
  SIRS in the presence of documented or suspected infection with organ dysfunction. Using an appropriate clinical algorithm (e.g. NEWS2 criteria of 5 or more or SOFA score of 2 or 2+ from baseline) or appropriate professional judgment.
• Septic shock
  Sepsis presenting with decompensated vasculature. Presenting with MAP <65mmHg (quick identification and primary/community)
  Sepsis requiring vasopressors to maintain MAP above 65mmHg plus serum lactate >2mmol/L (inpatient)
• Compensatory anti-inflammatory response syndrome (CARS)
  A body-wide suppression of immune responses following overwhelming pathogen exposure

Question 21

There are concerns that focus on organ dysfunction may delay spotting some cases
UHNM implements the “flag” system to assess unwell patients: Produced by the UK Sepsis Trust

When do we think sepsis if an individual has suspected infection for patient with SIRS?

Answer 21

Question 22

Basics of diagnosis:
1- What are the basic things you can find out with NO/limited equipment?
2- What can we find out from the basic examination?

Answer 22

1- History - Sepsis is defined as documented or suspected infection. Ask if there is a suspected infection.

2-
- Altered mental state
- Rashes/mottling of skin
- Capillary refill time
- Temperature
- Heart rate (pulse)
- Respiratory rate
- O2 saturation and blood pressure

Question 23

Basics of diagnosis:
How can we confirm inflammatory and organ function variables to get a SOFA score?

Answer 23

• White cell count
• CRP

Question 24

What is the sepsis 6?

Answer 24

• Completing these simple steps inside one hour will double the patient’s chances of survival

Question 25

Conclusion

Answer 25

Question 26

All infectious diseases follow a common pathway. Can you remember what we have already learned about how patients arrive at a stage where they have symptoms? Drag and drop these into the correct order: 1 Exposure 2 Adhesion 3 Colonisation 4 Invasion 5 Replication and survival 6 Toxicity and disease

Answer 26

1 Exposure 2 Adhesion 3 Colonisation 4 Invasion 5 Replication and survival 6 Toxicity and disease

Question 27

What is the most likely consequence if an infection is not adequately controlled by the local immune system? Sepsis Systemic inflammatory response syndrome Septic shock

Answer 27

Systemic inflammatory response syndrome Feedback: Yes! The inflammatory mediators lead to systemic symptoms. It's not good, but it's not truly "bad" yet

Question 28

A systemic inflammatory response, known as SIRS, is identifiable in patients where a local infection (pneumonia, UTI, etc.) has resulted in spread of inflammatory mediators to the systemic circulation. Given this, which clinical items are important to help us spot it? Reduced white cell count Elevated serum C-reactive protein Decreased heart rate Positive blood culture Decreased temperature (below 36 degrees Celsius) Elevated white cell count Increased temperature (above 37.9 degrees Celsius)

Answer 28

A systemic inflammatory response, known as SIRS, is identifiable in patients where a local infection (pneumonia, UTI, etc.) has resulted in spread of inflammatory mediators to the systemic circulation. Given this, which clinical items are important to help us spot it? Reduced white cell count Elevated serum C-reactive protein Decreased temperature (below 36 degrees Celsius) Feedback: Well done for spotting this! As with WCC, a reduction in this can often indicate a worsening situation. Often assumed to be "no temperature, no infection" and with very poor outcomes. Elevated white cell count Feedback: An easy right answer here! Mobilisation of resting neutrophils is the most common reason for this in the days following an infection Increased temperature (above 37.9 degrees Celsius)

Question 29

How many people are recorded as dying from sepsis every year in the UK?

Answer 29

Around 50,000

Question 30

Okay, we have learned a lot about this on paper. That's NOT the same as seeing it first-hand. Let's try and put this together and come up with some decisions. You are the FY1 on the respiratory ward. You are called to a 71-year-old male patient. They have left lower lobe pneumonia and score 2 amber flags and 1 red flag for sepsis. What is the very first thing you should do? Start appropriate antimicrobials (as per MicroGuide) Start fluids (20mL/kg crystalloid) Get senior support Measure serum lactate Take two blood cultures

Answer 30

Get senior support