2008B10 Describe sepsis and describe the metabolic consequences of sepsis.

 

List:

·      Definitions

·      Metabolic effects

·      Organ system effects

 

Old definitions:

Systemic inflammatory response syndrome (SIRS)

≥2 of

1.    Temp > 38°C or <36°C

2.    HR > 90

3.    RR >20 or PaCO2 <32mmHg

4.    WCC >12 or <4 or >10% immature cells

Septicaemia

Systemic infection

Sepsis

Systemic infection + SIRS

Severe sepsis

Systemic infection + SIRS + hypotension

Septic shock

Systemic infection + SIRS + hypotension + end-organ dysfunction

 

New definitions:

Sepsis

Life-threatening organ dysfunction caused by a dysregulated host response to suspected or confirmed infection

Septic shock

Sepsis

mAP <65

Lactate >2

Despite adequate volume resuscitation

 

Metabolic effects:

Causes

·  Pathogen -> WBC activation -> cytokine release (TNF-α, IL1, IL6, IFN)

Overall

·  ↑Metabolic rate

·  ↑Insulin resistance

·  ↑Catabolism

Autonomics

·  Cytokines and baroreceptor reflex -> ↑medullary SNS output

Hormones

·  ↑Cortisol

·  ↑Insulin (resistance)

·  ↑ADH

·  ↑Catecholamines

·  ↓Thyroid hormones

Acid-base

·  Hypoperfusion -> ↓tissue pO2 -> ↑anaerobic metabolism, lactic acidosis

·  ↑Metabolic rate -> further ↑ anaerobic metabolism

Fluid

·  Vasodilation, capillary leak -> ↓plasma volume, ↑interstitial volume (e.g. APO)

Substrate

·  ↑[Glucose]

·  ↑[Lipids]

·  ↑[Ketones]

Liver

·  ↓Glucose uptake, ↑gluconeogenesis

·  ↑Proteolysis

·  ↑Lipolysis

·  ↑Ketogenesis

Skeletal muscle

·  ↓Glucose uptake, ↑gluconeogenesis

·  ↑Proteolysis

·  ↑Lipolysis

Adipose

·  ↑Lipolysis

 

Organ system effects:

Brain

·  Blood-brain-barrier disruption -> cytokine and pathogen effects -> delirium

·  mAP <50mmHg -> CNS ischaemic response -> ↑↑SNS -> ↑HR/contractility/SVR

Heart

·  Cytokines -> ↓inotropy +/- septic cardiomyopathy

·  SNS -> ↑contractility (predominates if pH >7.2), ↑HR

·  Acidosis: ↓inotropy (predominates if pH <7.2)

·  Risk of myocardial ischaemia: ↑demand, ↓supply

Vasculature

·  -Cytokines: vasodilatation, capillary leak, microvascular thrombosis -> ↓SVR

·  Acidosis: vasodilatation

·  SNS: vasoconstriction (partly offsets dilation)

Respiratory

·  ↑metabolic rate -> ↑VCO2 -> ↑VA

·  Capillary leak -> +/- pulmonary oedema, ARDS

Renal

Effects of hypotension

·  ↑renin, angiotensin, aldosterone

·  +/- Failure of autoregulation (if mAP <70mmHg)

·  +/- ATN (if severe, prolonged)

Haem

·  Cytokines -> ± platelet dysfunction / microvascular thrombosis / DIC

 

 

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