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

 

List:

·     Definitions

·     Overall effect

·     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

Infection -> dysregulated host response -> life-threatening organ dysfunction

Septic shock

·  Sepsis

·  mAP <65

·  Lactate >2

·  Despite adequate volume resuscitation

 

Overall effect:

Pathophysiology

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

o   Endothelial dysfunction (capillary leak, microvascular thrombosis)

o   Vasomotor dysfunction (vasodilatation, impaired autoregulation)

o   ↑Hypothalamic set-point -> ↑temp -> ↑metabolic rate (7% per 1°C)

o   ↑Cardiorespiratory activity -> ↑metabolic rate

->> Inadequate oxygen delivery

->> Organ dysfunction

Key features

·  ↑Inflammation

·  ↑Insulin resistance

·  ↑Metabolic rate

·  ↑Catabolic rate

 

Metabolic effects:

Autonomic

·  Cytokines -> ↑SNS output from brainstem

·  ↓mAP -> baroreceptor response -> ↑SNS output

Endocrine

Substrate mobilization:

·  ↑Cortisol

·  ↑Insulin (resistance)

·  ↑Catecholamines

·  ↓Thyroid hormones

Volume preservation:

·  ↑RAAS

·  ↑ADH

Acid-base

·  ↑Anaerobic metabolism -> ↑lactic acidosis due to

o   ↑Metabolic rate

o   ↓Tissue perfusion

Fluid

·  Vasodilation, capillary leak ->

o   ↓Blood volume -> ↓CO (relative) -> ↓tissue perfusion

o   ↑Interstitial volume (e.g. APO)

·  Hypovolaemia -> ↑ADH, ↑RAAS activity -> ↓urine output

Substrate

·  ↑[Glucose]: ↓cell uptake, ↑gluconeogenesis

·  ↑[Amino acids]: ↑gluconeogenesis in liver, muscle (-> critical illness myopathy)

·  ↑[Lipids]: ↑lipolysis in liver, subcut fat, muscle

·  ↑[Ketones]: ↑lipolysis in liver, ↑Acetyl-CoA : OAA

 

Organ system effects:

Brain

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

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

Heart

·  Cytokines -> ↓inotropy +/- septic cardiomyopathy

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

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

·  Supply/demand mismatch: risk of myocardial ischaemia

Vasculature

·  Cytokines: vasodilatation, capillary leak -> ↓SVR (can be profound)

·  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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