Page 588 - ACCCN's Critical Care Nursing

Multiple Organ Dysfunction Syndrome 565

The specific pathophysiological concepts of inflamma- including circulating cytokines, oxygen free-radicals and
tion, oedema and infection are discussed below. activated neutrophils, alter the structure of endothelial
cells, enabling larger molecules (proteins, water) to cross
INFLAMMATION into the extravascular space. 23,28 This response mechanism
improves supply of nutrient-rich fluid to the site of injury,
Inflammation is part of innate immunity, a generic
response to injury, and is normally an excellent mecha- but if this becomes systemic, fluid shifts can lead to hypo-
nism to localise injury and promote healing. 22,23 The basis volaemia, third-spacing (interstitial oedema) or affect
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of this immune response is recognition and an immedi- other organs (e.g. acute lung injury, ALI).
ate response to an invading pathogen without necessarily
24
having previous exposure to the pathogen. Neutrophils, INFECTION AND IMMUNE RESPONSES
macrophages, natural killer cells, dendrites, coagulation
and complement are the principal active components of Infection exists when there is one of the following: posi-
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the innate host response. 23 tive culture, serology, presence of polymorphonuclear
leucocytes in a normally sterile body fluid except blood,
The classic signs of inflammation are: and clinical focus of infection such as perforated viscus
or pneumonia. In sepsis, the most common sites of infec-
● pain
● oedema tion are the lungs (34–54%), intra-abdominal organs
30,31
● erythema and heat (from vasodilation) (15–28%) and urinary tract (5–10%). 29 The incidence
● leucocyte accumulation and capillary leak. 22,23 of bloodstream infections is 30–40%, although one-
third of cases with septic shock have negative blood
Nitric oxide and prostaglandins (e.g. prostacyclin), are cultures; one reason suggested for this is antibiotic
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the primary mediators of vasodilation and inflammation administration prior to sample collection. The type of
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at the injury site. Injured endothelium produces mole- infecting organism has also changed over time, with
cules that attract leucocytes and facilitate movement to Gram-positive bacteria predominant, accounting for at
the tissues. White blood cells accumulate by margination least one-third of pathogens in septic shock; Gram-
(adhesion to endothelium during the early stages of negative, fungal, viruses and parasitic organisms are also
inflammation) and neutrophils accumulate at the injury involved. The increasing incidence of resistant organ-
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site, where rolling and adherence to binding molecules isms, partially as a result of the indiscriminate use of
on the endothelium occurs with eventual movement antibiotics, is an ongoing concern.
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across the endothelium into the tissues. Different blood
components therefore escape the intravascular space and The immune response to infection has both non-specific
occupy the interstitial space where they play the main and specific actions, with inflammation and coagulation
role in successive phases of the inflammatory response. responses intricately linked in sepsis pathophysio-
23,24,33,34
The endothelium therefore plays a bidirectional mediat- logy. Tissue injury and the production of inflam-
ing role between blood flow and the interstitial space matory mediators lead to:
where inflammation mainly takes place. Macrophages, ● coagulation via the expression of tissue factor and
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neutrophils and monocytes are responsible for phagocy- factor VIIa complex (tissue factor pathway; the primary
tosis and the production of toxic free radicals to kill cascade for initiation of coagulation; previously
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invading pathogens. The complement system, a collec- termed the ‘extrinsic’ pathway) 28,33-35
tion of 30 proteins circulating in the blood, is also acti- ● coagulation amplification via factors Xa and Va,
vated, with plasma and membrane proteins acting as leading to massive thrombin formation and fibrin
adjuncts to inflammatory and immune processes. When clots (common coagulation pathway). 28,33
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activated by inflammation and microbial invasion, these
processes facilitate lysis (cellular destruction) and phago- Note that blood cell injury or platelet contact with endo-
cytosis (ingestion) of foreign material. 23,26 thelial collagen initiates the contact activation pathway
(previously termed the ‘intrinsic’ coagulation pathway). 33
Dysfunction of organ systems often persists after the
initial inflammatory response diminishes; this is largely
unexplained, although dysoxia (abnormal tissue oxygen PROCOAGULATION
metabolism and utilisation) has been implicated. 22,27 Tissue factor is a procoagulant glycoprotein-signalling
36
Hypoxia induces release of IL-6, the main cytokine that receptor, expressed when tissue is damaged or cytokines
initiates the acute phase response. After reperfusion of are released from macrophages or the endothelium
ischaemic tissues, tissue and neutrophil activation forms (see Figure 21.3). Prothrombin is formed, leading to
reactive oxygen species (e.g. hydrogen peroxide) as a thrombin and fibrin generation from activated platelets.
byproduct. These strong oxidants damage other mole- Resulting clots are stabilised by factor XIII and thrombin-
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cules and cell structures that they form, resulting in activatable fibrinolysis inhibitor (TAFI). 33,36 Fibrinolysis
water and sodium infiltrate and cellular oedema. is a homeostatic process that dissolves clots via the
plasminogen–tissue plasminogen activator (tPA)–plas-
OEDEMA min pathway (involving antithrombin, activated protein
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Oedema occurs as a consequence of alterations to tissue C [APC] and tissue factor pathway inhibitor). APC:
endothelium, with increased microvascular permeability ● reduces inflammation by decreasing TNF and NFκB
(‘capillary leak’). As noted earlier, many mediators, production