Clinical pathophysiology of meningococcal septicaemia

Increased Vascular Permeability

When meningococci invade the bloodstream, endotoxin is released from the bacteria.  This triggers an inflammatory response, with release of inflammatory mediators, which is directed against the endothelial surface lining the blood vessels. One of the main functions of the endothelium is regulation of vascular permeability, and disturbance of this function causes the endothelial lining to become 'leaky', allowing increased passage of protein and water from the intravascular to extra-vascular compartments, causing a 'capillary leak syndrome'. The patient becomes hypovolaemic due to reduction in circulating volume, thus reducing cardiac output.

In compensation for reduced circulating volume, heart rate and contractility increase, and perfusion to skin and the splanchnic circulation is reduced. Therefore signs of hypovolaemia in sepsis include:

• Tachycardia
• Tachypnoea
• Cool peripheries
• Reduced urine output
• Irritability or lethargy.

Note that in the early phases of septic shock blood pressure is maintained by these compensatory mechanisms. This means that early in shock, children are alert as blood flow to the brain is being maintained at the cost of the other organs.

Myocardial dysfunction

Endotoxin and inflammatory mediators (such as IL6)⁴¹, together with other poorly defined 'myocardial depressant factors' reduce myocardial contractility. In addition, a myocardial cytotoxic process causes myocardial cell necrosis.

Hypovolaemia and myocardial dysfunction contribute to progression of shock. In addition, nitric oxide and other vasoactive mediators cause a relative 'vasoparesis' and relative inotrope unresponsiveness.

Progression of shock leads to tissue hypoxia and capillary leak leads to pulmonary oedema resulting in tachypnoea and hypoxia.

Eventually, compensatory mechanisms fail and blood pressure falls. This is a late and serious sign in septic shock in children.

Disseminated intravascular coagulation

Endotoxin and the inflammatory response leads to activation of the coagulation cascade and down-regulation of anticoagulant and fibrinolytic pathways, leading to a procoagulant state. Clotting times are prolonged and thrombocytopenia occurs.

Microvascular thrombosis contributes to multiple organ failure and purpura fulminans.

Amputations:
When purpura fulminans occurs, some tissues are irreversibly destroyed due to thrombosis within the microvasculature, combined with vasoconstriction and ischaemia in peripheries. Haemorrhagic necrosis in skin and clotting in small vessels can lead to loss of skin, digits or limbs.