Septic shock

When observed in the setting of infection, the combination of hypotension, tachycardia, tachypnea, and
markedly elevated or decreased body temperature is suggestive of septic shock. Early sepsis is
characterized by peripheral vasodilation, a compensatory increase in cardiac output, and warm
extremities. Numerous cytokines are released in sepsis, resulting in widespread systemic inflammation.
One of the most important mediators of sepsis is tumor necrosis factor-alpha (TNF-a), an acute-phase
cytokine produced by activated macrophages. TNF-a stimulates systemic inflammation via recruitment
of additional leukocytes (eg, neutrophils, macrophages) and increasing pro-inflammatory cytokine
production. Other cytokines responsible for inducing the systemic inflammatory response in sepsis
include IL-1 and IL-6.
--- IL-3 is a cytokine produced by activated T cells. It stimulates the growth and differentiation of stem
cells in the bone marrow.
--- IL-4 is a cytokine produced by Th2 T-helper cells. It stimulates the growth of B cells and increases the
number of Th2 T-helper cells at the site of inflammation.
--- IL-10 is an anti-inflammatory cytokine produced by macrophages and Th2 T-helper cells. IL-10 limits
the production of pro- inflammatory cytokines (eg, interferon-gamma, IL-2, IL-3, TNF-a).
--- Leukotriene B4 is a metabolite of arachidonic acid. Its main function is to stimulate neutrophil
migration to the site of inflammation.
--- Transforming growth factor-beta is released by macrophages and has anti-inflammatory roles in
sepsis, including suppressing the release of IL-1 and TNF-a, and inhibiting lymphocyte proliferation.
Educational objective:
Tumor necrosis factor-alpha is released from activated macrophages and is one of the most important
mediators of the systemic inflammatory response in sepsis. Other cytokines responsible for inducing the
systemic inflammatory response include IL-I and IL-6.

Septic shock

This patient with fever, cough, and radiologic evidence of consolidation in the right lower lung has
pneumonia. Her tachycardia, hypotension and confusion (evidence of end-organ hypoperfusion)
are most likely due to septic shock, which is characterized by increased permeability of the vascular
endothelium with leakage of intravascular fluid into the extravascular space.
In the management of septic shock, rapid restoration of intravascular volume and adequate end-
organ perfusion is critical. This is best accomplished with the administration of boluses of isotonic
 crystalloid in the form of 0.9% (normal) saline or lactated Ringer solution through large-bore,
peripheral intravenous catheters. These solutions are ideal for volume resuscitation because they
have osmolarity very close to the normal osmolarity of the blood (—285 mOsm/kg H20), while the
sodium and chloride ions help retain the fluid in the extracellular space Prompt initiation of
appropriate empiric antibiotic therapy is also critical in the management of septic shock
---- 0.45% (half-normal) saline is hypotonic; 5% dextrose in 0.45% saline is hypertonic initially but
becomes hypotonic following infusion because the dextrose is rapidly metabolized. These hypotonic
solutions are often used at low infusion rates for patients with a deficiency of free water (ie,
hypernatremia) or for maintenance hydration. However, they are not effective for rapid volume
resuscitation because the low osmolarity causes much of the fluid volume to shift into the
intracellular space following infusion.
--- Infusion of 3% (hypertonic) saline can lead to rapid fluid-shifting from the intravascular to the
extravascular space with potentially devasting consequences (eg, osmotic demyelination syndrome);
therefore, 3% saline is not appropriate for rapid volume resuscitation. It is appropriate for careful
use in patients with severe symptomatic hyponatremia.
---- Albumin solution is an isotonic colloid solution that can be used for rapid volume resuscitation.
However, it is less preferred due to high cost and limited availability compared to isotonic
crystalloid.
---Sodium bicarbonate solutions can have variable tonicity and are typically used at low infusion
rates for patients with severe metabolic acidosis. These solutions are generally not used for rapid
volume resuscitation.
Educational objective:
The initial management of septic shock requires rapid fluid resuscitation to replace intravascular
volume and restore adequate end-organ perfusion. This is best accomplished with intravenous
boluses of isotonic crystalloid in the form of 0.9% (normal) saline or lactated Ringer solution
because these solutions remain in the extracellular space.

Septic shock
This patient with fever, dysuria, flank pain, and right costovertebral angle tenderness likely has
pyelonephritis. In addition, her hypotension in the setting of infection suggests septic shock.Septic
shock is the most common type of distributive shock; other types include anaphylactic shock and
neurogenic shock.

The primary disturbance in septic shock is widespread vasodilation leading to decreased systemic
vascular resistance (SVR). Increased vascular permeability (third-spacing) and peripheral venous dilation
also cause a reduction in central venous pressure and pulmonary capillary wedge pressure (PCWP) ).
Initially, the hypotension and inflammation from sepsis trigger a compensatory increase in sympathetic
drive that increases heart rate and myocardial contractility, leading to increased cardiac index (cardiac
output per body surface area). The high blood flow rates prevent complete extraction of oxygen by the
tissues, resulting in high mixed venous oxygen saturation. As shock progresses, tissue ischemia and
accumulation of cytotoxic mediators eventually cause a reduction in cardiac output with end-organ
dysfunction.
---- Low cardiac index with high PCWP is consistent with cardiogenic shock .The primary disturbance is
typically left ventricular failure with a compensatory increase in SVR in an effort to maintain adequate
blood pressure for organ perfusion .

---- Low PCWP with low cardiac index and high SVR occurs in both hypovolemic shock and some types of
obstructive shock (eg, pulmonary embolism, tension pneumothorax). Central venous pressure is low in
hypovolemic shock and high in obstructive shock .
---- Low PCWP with low cardiac index and low SVR occurs in neurogenic shock. As in sepsis, the primary
disturbance is peripheral vasodilation. However, due to nerve injury there is no sympathetic-mediated
increase in heart rate and myocardial contractility; therefore, cardiac output is low
Educational objective:
Septic shock causes widespread arteriolar vasodilation, which leads to a decrease in systemic vascular
resistance and a compensatory increase in cardiac output Central venous pressure and pulmonary
capillary wedge pressure are also decreased due to pooling of blood in the dilated veins. Increased flow
rates through the peripheral capillaries lead to incomplete oxygen extraction by the tissues and high
mixed venous oxygen saturation.

Septic shock
This woman is suffering from septic shock Septic shock results from the release of endotoxins into the
bloodstream. Regardless of the bacterial source, most mammals, including humans, experience the
same range of toxic, biological effects as a result of these endotoxins.
Endotoxins are found in the outer membrane of Gram-negative bacteria, which is composed of
lipopolysaccharide (LPS). LPS is released during destruction of the bacterial cell wall. It can also be
released during cell division. LPS is a very long, heat-stable molecule arranged into three
regions: O antigen, core polysaccharide, and Lipid A. Lipid A is responsible for the toxic properties of LPS
that lead to Gram-negative sepsis and endotoxic septic shock
Lipid A induces shock by activation of macrophages and granulocytes. This activation results in the
synthesis of endogenous pyrogens, such as IL-I , prostaglandins, and the inflammatory mediators: tumor
necrosis factor-alpha (TNF-aIpha) and interferon. These cytokines then induce a febrile response by the
action of IL-I on the hypothalamus, as well as hypotension, increased vascular permeability with third-
spacing of fluids, diarrhea, disseminated intravascular coagulation, and death
--- E coli strains that cause neonatal meningitis synthesize K-I capsular antigens.
----Heat-stable exotoxin is one of the enterotoxins produced by ETEC.
---- The O antigen is a cell wall outer membrane polysaccharide antigen used to classify gram-negative
bacteria.
--- Fimbriae, or pili, are a virulence factor that allow bacteria to adhere to the target tissue and establish
infection. Examples of organisms that use pili are Neisseria meningitidis, uropathogenic and
diarrheogenic E. coli, Bordetella pettussis, and Vibrio cholerae.
----Flagellar (H) antigen is a heat-labile protein which is one component of the serologic classification of
the enterobacteriaceae.
Educational Objective:
Gram-negative sepsis is caused by the release of LPS from bacterial cells during division or by
bacteriolysis; LPS is not actively secreted by bacteria. Lipid A is the toxic component of LPS, it causes
activation of macrophages leading to the widespread release of IL-I and TNF-alpha,
which cause the signs and symptoms of septic shock: fever, hypotension, diarrhea, oliguria, vascular
compromise, and DIC.