Sepsis which is commonly called as septicemia is one of the most dreadful and vulnerable life threatening disease which is quite uncommon in popularity. Around the world 1.8 million cases and in India there is 30% of nosocomial infectious patients get infected per annum accounted epidemiologically. It happens by gradual steps which is based on the incidence of the physiological and biochemical malfunctions from which septic shock is the last severe step. It is not depend on the single specific pathway dysregulation rather regulated by multi biological pathways. Various malfunctions in regulated systems like paralysis of neutrophils, higher production of proinflammatory products, diversion of adaptive immune cells like TH1 and TH2, apoptosis of lymphocytes and dendritic cells leads to sepsis. Complement anaphylatoxin C5a plays a major mediator of inflammatory response and dysregulation of plasmatic cascade. Disruption of any connecting linkers between the coagulation, complement and fibrinolysis leads to inhibition of anticoagulation mechanism. Adrenergic and cholinergic inflammatory pathway which regulates the inflammatory response get altered. In biochemical point of view endothelial dysfunction occurs mainly due to the formation of reactive oxygen species (ROS) and other components, Properdin level also get downregulated. Although much progress has been made in the treatment of inflammatory disease, the continued high mortality in septic shock is a sobering reflection of current therapeutic approaches. Nevertheless, increased understanding the molecular mechanism of various factors, connecting links and the multi effectors of sepsis can provide for better path to conquer sepsis in maximum ways.
2. The fact that there is no such thing as a perfect anti-sepsis does
not mean that one might as well do brain surgery in a sewer.
Robert M. Solow
3.
4. It is a one of the most vulnerable life threatening
emergency and because of which more than 1
million cases happens in India. Even in America
too more than 258000 peoples suffers each year.
5. Sepsis is a life threatening condition that arises when the
body’s response to infection injures its own tissues and
organs.
It may caused by a combination of factors related to the
particular invading pathogens and to the status of the
immune system of the host.
Sepsis is ‘difficult to diagnose’ because it happens quickly
and can be confused with other conditions.
24. WORLDWIDE
1.8 million cases annually
EUROPEAN UNION
90.4 cases of severe
sepsis per 100000 people
UNITED KINGDOM
100000 cases of severe
sepsis each year with
about 37000 deaths
25. The Indian Journal of critical care medicine came out
with a study that found nearly 30% of the patients in
the India ICU suffered severe sepsis or a high level of
septic shock.
35. Generation of complement anaphylatoxin C5a by activation of complement system and C5 convertase activity
of thrombin of the coagulation cascade.
C5a triggers release of pro-inflammatory mediators including macrophage migration inhibitory factors (MIF)
and high mobility group box 1 protein (HMBG1) etc. which activates the coagulation cascade by inducing
tissue factor expression.
HMGB1 is a pleiotropic cytokine that binds to toll like receptor 4 (TLR4) and acts as an endogenous alarmin to
increase the release of pro-inflammatory mediators.
TLR4 mediated response are negatively regulated by C5a.
Large amounts of HMBG1 and MIF which promotes a proinflammatory response by amplifying cytokine
secretion through the upregulation of TLR4 expression.
MIF which is produced by the pituitary gland and by leukocytes inhibits the anti-inflammatory effects of
indigenous glucocorticoids of the endocrine system which induces MIF secretion.
HMBG1 links the immune response with the autonomic nervous system, which regulates the release of
HMBG1 and other cytokines during sepsis.
Interleukin-17A (IL-17A), which is an important regulator of inflammation at the interface between innate and
adaptive immunity, orchestrates responses of both innate and adaptive immune cells.
48. Breakdown of endothelial barrier function.
Loss of fluid into extravascular space leads to edema in the lungs, kidney
and brain.
Increase of endothelial permeability induced by TNFα and LPS by enzymatic
cleavage of adherence junction proteins.
Inflammation due to alteration of reaction oxygen (ROS), nitrogen species
including O₂⁻, H₂O₂, OHˉ, NO.
Initiation of lipid peroxidation, direct inhibition of mitochondrial respiratory
chain enzymes, inactivation of glyceraldeyde-3 phosphate dehydrogenase,
inhibition of membrane Na⁺/ K⁺ ATPase activity, inactivation of membrane
Na⁺ channels and other oxidative protein modifications.
No functions as both as autocrine and paracrine cellular mediator,
vasodilator, inhibits platelet aggregation and smooth muscle cell
proliferation, decrease the expression of proinflammatory molecules by the
endothelium.
NO normally produced in the endothelium by endothelial NO synthase, an
enzyme that is constitutively expressed.
During the pathogenesis of sepsis changes in the expression of
coagulation-involved factors. A dysregulated balance of tissue-type
plasminogen activator and plasminogen activator inhibitor-1 leads to
increased coagulation and suppressed fibrinolytic activity.
In meningococcal sepsis, thrombomodulin and endothelial protein C
receptor are lacking. With the occlusion of micro vessels by microthrombi a
lack of nutrients and hypotoxic conditions develop in the tissue contributing
decisively to organ failure.
49. Properdin is a normal serum protein that increases the production of
complement activation products by binding C3b integral to convertage
complexes and amplifying their activity at the site of activation.
In case of sepsis , circulating complement C3 concentrations are decreased,
through C3 is described as a positive acute phase reactant.
50.
51. Flash capillary
refill, mental
status with fabric
illness, co-
morbidities in
children
Broad
spectrum
and β-lactam
antibiotics
Crystalloid
solutions and
albumin, packed
red blood cells are
recommended
Norepinephrine,
epinephrine,
vasopressin,
dobutamin
Glucocorticoids
should be used in
critical illness.
52. Sepsis consists of a broad spectrum conditions
along a continuum. Throughout the world sepsis
occurrence and mortality rates are high amongst
children. It is important that prehospital healthcare
providers, such as paramedics, can quickly identify
and commence appropriate management to ensure
the child has the best possible chance of recovery. It
has been proven that delays in treatment have a
highly detrimental effect on the outcomes so it is
important these delays are reduced. Early goal
directed therapy has been key focus of recent sepsis
research and is the guiding principle behind the
surviving sepsis guidelines developed by an
International conference (Dellinger et al, 2013).