pathophysiology
Pathophysiology of sepsis
The pathophysiology of sepsis is extremely complex and mechanisms of multiple
organ system dysfunction and immune system alterations are reviewed here
Francisco Valenzuela
Sánchez
Department of Critical
Care Medicine, University
Hospital SAS of Jerez,
Jerez de la Frontera,
Cadiz, Spain
Blanca Valenzuela
Méndez
Gynecology and
Obstetrics Departament,
Universitary Hospital
Germans Trias i Pujol;
Department of Medicine,
Universitat Autónoma
de Barcelona, Barcelona,
Spain
Juan Francisco
Rodríguez Gutiérrez
Hematology Department,
University Hospital SAS of
Jerez, Jerez de la Frontera,
Cadiz, Spain
Jordi Rello MD PhD
CIBERES, Barcelona.
Vall d´Hebron Institut
of Research (VHIR),
Universitat Autónoma
de Barcelona, Barcelona,
Spain
Sepsis is an uncontrolled inflammatory response
induced by infection. 1 The innate immune system
is the first line of defence against an infectious
insult, which conditions the adaptive response
with the objective of neutralising the
aggressor(s). At the same time, a compensatory
anti-inflammatory response and the process of
repairing tissue damage is generated. 2 If this
inflammatory response goes beyond the local
level, it becomes a systemic reaction, with
potentially catastrophic results. Added to this
are the characteristics of the micro-organisms and
of the host, which also affect the manifestation
of sepsis. 3
Due to mechanisms that have not been fully
clarified, a series of cellular alterations occur that
lead to organ failure and that constitute the basis
of the organ dysfunction, the basis of the current
concept of sepsis in the Sepsis-3 consensus
conference. 4
Alteration of the immune function in sepsis
Innate immunity
The innate immune system is the first line of
defence against pathogens and comprises physical
and chemical barriers, cells and circulating
effector proteins. In inflammatory activation,
damage-associated molecular patterns (DAMPs),
of both micro-organisms (PAMPs) and endogenous
products from damaged tissues (alarmines), are
recognised through host molecules called pattern
recognition receptors (Figure 1), the most notable
members of which are the Toll-like receptors
(TLR). 1–3 The binding of a TLR to a specific ligand
results in activation of a series of adaptor proteins
present in the cell cytoplasm (Table 1). 5–7
Activation of NK-κB
Following this, nuclear factor kappa-light-chain-
enhancer of activated B cells (NF-κB) binds to
various promoters to activate the transcription
figure 1
Sequence of inflammatory activation due to bacterial infection
and its evolution into acute organ injury
Neutrophil chemotaxis
Host cell
Apoptosis
DAMPs
N-formyl peptides
Mitochondrial DNA
FPR1
TLR9
p38 MAPK
Neutrophil
PAMPs
Bacterial DNA
N-formyl peptides
Acute
injury
TLR9
FPR1
Bacteria
Neutrophil chemotaxis
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HHE 2018 | hospitalhealthcare.com