Rate of development of obstruction to blood

flow response:
• acute, massive PE involving 2 or more lobar arteries and 50%
pulmonary bed can
cause shock (sPAP max 50 mm Hg) but chronic PE can cause
> 75% obstruction
without shock (sPAP 100 + mm Hg)
•
acute cardiac tamponade can occur with 150 mL fluid but over
2L can be well
•
acute
cardiac
tamponade
can
occur
with
150
mL
fluid
,
but
over
2L
can
be
well
tolerated if slow accumulation
Similar variability based on presence of pre-
existing
cardiopulmonary disease
cardiopulmonary
disease
Distributive Shock

A
na
p
h
y
lactic shock:
immediate h
yp
ersensitivit
y
reaction
py
yp y
mediated by the interaction of IgE on mast
cells and basophils
with the appropriate antigen resulting in
mediator cascade
Anaphylactoid reactions
involve similar release of mediators
via non-immunologic mechanisms.
Primary mediators include histamine,
serotonin, eosinophil
chemotactic factor, and proteolytic enzymes.
S d di t i l d PAF b d ki i t l di
S
econ
d
ary me
di
a
t
ors
i
nc
l
u
d
e
PAF
,
b
ra
d
y
ki
n
i
n, pros
t
ag
l
an
di
ns,
and leukotrienes.
Distributive Shock
Anaphylactic shock Anaphylactoid shock
insect envenomations
antibiotics (beta-lactams,
vancomycin, sulfonamides)
ionic contrast media
protamine
o
p
iates
heterologous serum (anti-toxin,
anti-sera)
blood transfusion
p
polysaccharide volume
expanders (dextran,
hydroxyethyl starch)
immunoglobulins (esp IgA
deficient)
Egg-based vaccines
muscle relaxants
anesthetics
latex
Pathophysiology distributive shock

In distributive shock, the inadequate tissue perfusion is caused by loss of the normal
responses of vascular smooth muscle to vasoconstrictive agents coupled with a direct
vasodilating effect. The net result in a fluid-resuscitated patient is a hyperdynamic,
hypotensive state associated with increased mixed venous O2 saturation; however, evidence
of tissue ischemia as manifest by an increased serum lactate, presumably due to intraorgan
functional shunts.

Early septic shock (warm or hyperdynamic) causes reduced diastolic blood; widened pulse
pressure; flushed, warm extremities; and brisk capillary refill from peripheral vasodilation,
with a compensatory increase in cardiac output. In late septic shock (cold or hypodynamic),
myocardial contractility combines with peripheral vascular paralysis to induce a pressure-
dependent reduction in organ perfusion. The result is hypoperfusion of critical organs such as
the heart, brain, and liver.

The hemodynamic derangements observed in septic shock and SIRS are due to a complicated
cascade of inflammatory mediators. Inflammatory mediators are released in response to any
of a number of factors, such as infection, inflammation, or tissue injury. For example,
bacterial products such as endotoxin activate the host inflammatory response, leading to
increased pro-inflammatory cytokines (eg, tumor necrosis factor (TNF), interleukin (IL)–1b,
and IL-6). Toll-like receptors are thought to play a critical role in responding to pathogens as
well as in the excessive inflammatory response that characterizes distributive shock; these
receptors are considered possible drug targets.

Cytokines and phospholipid-derived mediators act synergistically to produce the complex

alterations in vasculature (eg, increased microvascular permeability, impaired microvascular
response to endogenous vasoconstrictors such as norepinephrine) and myocardial function
(direct inhibition of myocyte function), which leads to maldistribution of blood flow and
hypoxia. Hypoxia also induces the upregulation of enzymes that create nitric oxide, a potent
vasodilator, thereby further exacerbating hypoperfusion.

The coagulation cascade is also affected in septic shock. In septic shock, activated monocytes
and endothelial cells are sources of tissue factor that activates the coagulation cascade;
cytokines, such as IL-6, also play a role. The coagulation response is broadly disrupted,
including impairment of antithrombin and fibrinolysis. Thrombin generated as part of the
inflammatory response can trigger disseminated intravascular coagulation (DIC). DIC is
found in 25-50% of patients with sepsis and is a significant risk factor for mortality.[2, 3]

During distributive shock, patients are at risk for diverse organ system dysfunction that may
progress to multiple organ failure (MOF). Mortality from severe sepsis increases markedly
with the duration of sepsis and the number of organs failing.

In distributive shock due to anaphylaxis, decreased SVR is due primarily to massive

histamine release from mast cells after activation by antigen-bound immunoglobulin E (IgE),
as well as increased synthesis and release of prostaglandins.

Neurogenic shock is due to loss of sympathetic vascular tone from severe injury to the
nervous system.