Pathogenesis sepsis

Question 1

Define sepsis

Answer 1

Sepsis is the systemic inflammatory response to infection leading to organ dysfunction

Life-threatening organ dsyfunction= increase in SOFA score from 2+ from baseline.

Question 2

Define SIRS

Answer 2

Systemic inflammation response syndrome

Features
 Fever- greater than 38
 Tachypnoea- greater than 20 breaths per minute
 Tachycardia - greater than 90 beats per minute
 Leucocytosis/ leucopenia or leukopenia- greater than 12,000 or less than 4000.
 Proven or probable infection

Question 3

Problems with SIRS

Answer 3

• Too sensitive: Healthy patients have normal response to infection
• Too non specific: Many SIRS patient may not have an infective process
• Infection category is too vague

Question 4

Define septic shock

Answer 4

Lack of tissue perfusion, leading to organ failure due to systemic inflammatory response to infection

Question 5

Immunopathology of sepsis

Answer 5

Widespread recognition of generic microbial elements triggers proinflammatory response.

Proinflmmatory cytokines (IL-1, TNF g, TNF a)
leads to
- Coagulation
- Neutrophil migration and adhesion
- Cardiovascular changes
- Metabolic changes
- Increased vascular permeability and decreased resistance,

Question 6

Coagulation changes in sepsis

Answer 6

Triggered by release of proinflammatory cytokines

• Platelet activation
• Activation of coagulation cascades (inflammatory):

Extrinsic pathway which involves tissue factor , intrinsic pathway which involves contact . All ultimately leads to the formation of a fibrin clot. Causing microvascular thrombosis.

• Down regulation of anticoagulation mediators (Anti inflammatory)
• Consumption of coagulation factors= consumption Coagulopathy.

Question 7

Cardiovascular changes in sepsis.

Answer 7

• Decreased contractility
  1. Early distributive shock from peripheral vasodilation
  2. Hypovolemic shock due to capillaries leaking, low filling pressure.
  3. cardiogenic shock from cardiac myocyte suppression and high filling pressure

Question 8

metabolic changes in sepsis

Answer 8

• Protein catabolism
• Insulin resistance
• Decreased uptake of oxygen into tissue tissue hypoxia then lactic acidosis (low pH, high lactate)

Question 9

Most common gram negative cause of sepsis

Answer 9

E.coli

Then Klebs

Question 10

Gram positive sepsis

Answer 10

Common causes: s.aurea, s pyogenes

No LPS so activation of immune response is triggered by

• peptidoglycan
• lipoteichoic acid

Superantigens can trigger 20% of resting T cells, causes non-specific response to cells.

Question 11

Strepticoccal toxic shock syndrome cause

Answer 11

S pyogenes, Group A

Question 12

SOFA score

- Features

Answer 12

Assesses sepsis by looking at different function of six organ systems
- Mainly used in ICU

Features

• Cardiovascular- blood pressure
• Renal: urine output/ creatinine.
• CNS: GCS
• Resp: O2 sats,
• Liver: bilirubin levels
• Coagulation: platelet levels.

Question 13

qSOFA scores

Answer 13

Assess organ dysfunction outside of ICU

Organ dysfunction when (2+)

• Tachypnoea >22
• GCS <15
• SBP <100.

Question 14

Initial antibiotic therapy

Answer 14

IV empirical broad spectrum of 1+, within one hour (golden hour)

Examples

• Ceftriaxone + gentamicin + metronidazole
• Co-amoxiclav. + gentamicin
• Coamoxiclav + amikacin
• Teicoplanin, gentamicin

Review antibiotics in <72 hours via results from blood culutures etc, then start focused antibiotics.