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Question 391
Pathology → General
Classification
Question
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During septic shock, bacterial lipopolysaccharide-binding protein activates macrophages, leading to release of TNF-alpha and IL-1 and activation of several inflammatory systems. Which downstream haemodynamic sequence best explains progression to tissue hypoperfusion?
Question Stem
Select the single best answer.
Options
A
Generalised vasoconstriction → reduced vascular permeability → increased circulating volume
B
Vasodilatation and increased vascular permeability → fluid and protein leakage → reduced effective circulating volume and impaired microcirculatory perfusion
C
Reduced inflammatory mediator release → capillary closure → sustained hypertension
D
Isolated myocardial hypertrophy → increased cardiac output → tissue hyperoxia
E
Reduced endothelial permeability → intravascular fluid retention → increased tissue perfusion
Explanation
In septic shock, microbial products activate macrophages and inflammatory mediators including TNF-alpha and IL-1. Vasodilatation and increased vascular permeability initially contribute to a hyperdynamic circulation, followed by fluid and protein leakage, reduced effective circulating volume, sludging and impaired tissue perfusion. Coagulation activation may also contribute to DIC.
Option Validity
A) Septic shock is characterised by vasodilatation and increased rather than reduced vascular permeability.
C) The syndrome is driven by substantial inflammatory mediator activation and does not characteristically produce sustained hypertension through reduced mediator release.
D) Myocardial hypertrophy is not the mechanism producing the acute septic microcirculatory failure described.
E) Increased, not reduced, endothelial permeability contributes to intravascular fluid and protein loss and impaired perfusion.
Further Reading
Saxena R. Textbook for MRCOG-1. Chapter 5: Pathology. General Pathology, pp.161–175.