3 CE Credits

Shock Pathophysiology
Elizabeth Thomovsky, DVM, MS, DACVECC
Paula A. Johnson, DVM
Purdue University

Abstract: Shock, defined as the state where oxygen delivery to tissues is inadequate for the demand, is a common condition in
veterinary patients and has a high mortality rate if left untreated. The key to a successful outcome for any patient in shock involves
having a clear understanding of the pathophysiology and compensatory mechanisms associated with shock. This understanding
allows more efficient identification of patients in shock based on clinical signs and timely initiation of appropriate therapies based
on the type and stage of shock identified.

S
hock is a condition that is commonly seen in practice but
Anaerobic metabolism
just as commonly is not completely understood. This review
focuses on the body’s compensatory responses to shock and Production and release of lactate, cytokines, prostaglandins, nitric oxide, etc.
the clinical signs to help provide practitioners with a better under-
standing of what shock is and how it can be categorized. Treatment is
discussed in the context of E,the
ThomovskyThomovsky
pathophysiology
E, etpathophysiology.
et al. Shock
but is not
al. Shock pathophysiology.
covered
Compend Contin
Compend Contin Cellular swelling
Increased capillary Decreased vasomotor tone
permeability
in depth. Educ Vet 2013;35(8).
Educ Vet 2013;35(8).

Definitions Interstitial edema

The first difficulty comes in defining shock. At its most elemental,

the definition can be stated as: Cellular dysfunction
Circulatory collapse
oxygen delivery ≠ oxygen consumption (DO2 ≠ VO2). 1

GI barrier breakdown + translocation of

gut bacteria

Glucose Glucose Consumptive coagulopathy

Anaerobic Anaerobic
Metabolism. Metabolism.
Pyruvate Pyruvate
Aerobic Metabolism.
Aerobic Metabolism. cannot entercannot entercycle
the TCA the TCA cycle and enters
and enters
Pyruvate isPyruvate is able to enter
able to enter the Cori
the Cori cycle cycle
to form to form
lactate. lactate. Lactate
Lactate
the TCA
the TCA cycle and iscycle and is can be usedcanbybetheused
brainbyand
theheart
braininand heart in Death
converted
converted into large into large the short
the short term term for
for energy, butenergy,
it is but it is
amounts ofamounts
ATP. of ATP. overall an inefficient
overall an inefficient source of source ofFigure 2. Sequelae of prolonged anaerobic metabolism.
2 pyruvate 2 pyruvate cellular energy.
Figure 2. Sequelae of prolonged anaerobic metabolism.
cellular energy.

Oxygen Oxygen
Oxygen Oxygen Most cases of shock are the result of decreased delivery of blood
to tissues. When blood is not delivered to tissues, oxygen is not
delivered. Oxygen is critical for normal cellular function; when the
TCA cycleTCA cycle Cori cycle Cori cycle tissues do not receive oxygen, normal cellular aerobic metabo-
lism ceases and anaerobic metabolism ensues. As a result, cells are
unable to produce adequate amounts of ATP (FIGURE 1) to sustain
normal metabolic function, ultimately leading to cellular dysfunc-
tion and death. Additionally, sustained anaerobic metabolism results
2 lactate 2 lactate
in the production of cytokines and substances such as lactate and
36 36 2 2
ATP ATP nitric oxide, which further complicate shock (FIGURE 2).
ATP ATP
Multiple factors determine oxygen delivery to cells (FIGURE 3);
however, the simplest way to envision oxygen delivery is to consider
the body’s cardiac output as being roughly equivalent to the blood
Figure 1. Aerobic versus anaerobic metabolism. TCA = tricarboxylic acid
delivered throughout the body. In turn, cardiac output is defined
Figure 1. Figure
Aerobic1.versus
Aerobic versus anaerobic
anaerobic metabolism.
metabolism. TCA = tricarboxylic
TCA = tricarboxylic acid. acid.

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 Thomovsky E, et al. Shock pathophysiology. Compend Contin Educ Vet 2013;35(8).
Shock Pathophysiology

DO2 = CaO2 x CO It is less common that the body’s demand for oxygen is the
driving force for the imbalance (i.e., that cardiac output is com-
Preload
Afterload pletely normal in a patient in shock). One example of this situation
Contractility
is overwhelming infection, in which the infection causes increased
cellular metabolism (and therefore increased cellular oxygen
CO = HR x SV demand). Increases in cellular metabolism alone can cause a state
of shock before or in addition to the development of decreased
cardiac output secondary to the infection.1,2
CaO2 = (SpO2 x 1.34 x [Hb]) + (0.003 x PaO2) A second example in which cardiac output can be normal in a
Figure 3. The determinants of oxygen delivery in the body. CaO2 = arterial oxygen shock patient is when there is abnormal perfusion of tissues.
content, CO = cardiac output, DO2 = oxygen delivery, [Hb] = concentration of When large numbers of cells are bypassed by oxygenated blood, an
hemoglobin in the blood, HR = heart rate, PaO2 = partial pressure of oxygen in imbalance
Figure 3. The determinants of oxygen delivery in the body. CaO = arterial oxygen content, CO =cardiac output, DO = oxygen delivery, [Hb] =in oxygen demand and delivery develops that can lead
arterial blood, SV =stroke volume, SpO2 =rate, % hemoglobin
2
saturation with oxygen. 2
concentration of hemoglobin in the blood, HR = heart 2
to shock.
PaO = partial pressure of oxygen in arterial blood, SV =stroke volume,
2 SpO = %1,3–8
In cases of abnormal perfusion, the microcirculation
hemoglobin saturation with oxygen.
at the capillary and other small (≤100 µm) vessel level is typically
as heart rate times stroke volume. Appreciating the interrelationship affected.2,4,7 The microcirculation responds in a variety of ways,
between oxygen delivery and cardiac output is critical to under- culminating in increased permeability of the walls of the endo-
standing the pathophysiology of shock and guiding treatment. thelium and regions of vasodilation and altered blood flow.4 This

Table 1. Categories, Examples, Basic Definitions, and Pathophysiology of Shock

Category of Shock Classic Example Basic Definition Pathophysiology/Events Leading to Shock

Hypovolemic Decreased effective circulating blood Decreased effective circulating volume à decreased venous
volume return à decreased stroke volume à decreased cardiac
Absolute Absolute: bleeding output and blood delivery to tissues
from wound (laceration)
Relative Relative: bleeding into
third space in body
(hemoabdomen,
fracture hematoma)

Obstructive Gastric-dilatation Physical impediment to blood flow in Physical blockage to venous return/blood trapped distal to
volvulus (dilated large vessels (predominantly veins) obstruction à decreased stroke volume à decreased
stomach occludes cardiac output and blood delivery to tissues
caudal vena cava)

Cardiogenic Dilated cardiomyopathy Heart unable to pump blood (typically Decreased contractility à decreased cardiac output and
caused by lack of contractility) blood delivery to tissues

Distributive Sepsis (Gram-negative Multifactorial (one or more of the following):

endotoxemia)
1. Vasodilation, especially peripheral Macrocirculatory vasodilation à blood trapped in periphery
Anaphylaxis vessels (both microcirculation + à decreased venous return à decreased stroke volume à
macrocirculation) decreased cardiac output and blood delivery to tissues
Microcirculatory vasodilation à oxygen arrives at the
tissues but is not delivered to the metabolizing cells due to
vasodilation-driven shunting of blood away from the cells

2. Increased vessel permeability Increased vessel wall permeability à decreased effective

(relative hypovolemia as fluid leaks circulating blood volumeà decreased venous return à
out of vessels) decreased cardiac output and blood delivery to tissues

3. Decreased cardiac contractility due Decreased cardiac contractility à decreased cardiac output
to effects of cytokine mediators and blood delivery to tissues
(sepsis) or platelet activating factor
(anaphylaxis)

4. Activation of the coagulation Multiple clot formation à small vessels occluded à

system decreased venous return à decreased cardiac output and
blood delivery to tissues

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 Shock Pathophysiology
Thomovsky E, et al. Shock pathophysiology. Compend
Contin Educ Vet 2013;35(8).

leads to less blood being delivered to

other cells and local hypoxia of the by- Shock (decreased
passed cells. Examples of such derange-
Decreased baroreceptor cardiac output)
activity (aortic and
ments in microcirculation include the carotid bodies)

systemic inflammatory response syn-

↑[Na] (osmoreceptors);
drome (SIRS) and reperfusion injury.4 Decreased decreased blood volume
Additionally, in human medicine, use of Increased SNS
tone
baroreceptor (baroreceptors)
activity (JG
coronary artery bypass grafting can apparatus)
physically re-route blood away from tis- Adrenal V1 receptors
gland Release antidiuretic
sues, causing those tissues to suffer from hormone/ vasopressin
Epinephrine/
decreased oxygen delivery.4 norepinephrine Renin release (posterior pituitary)
release (kidney)
In an attempt to encompass and cate-
V2 receptors
gorize the various types of shock, shock is β1 receptors α receptors
bloodstream
typically divided into categories that help Insert aquaporin
channels collecting
explain why oxygen delivery is not match- Increased heart Vaso- and veno- Angiotensinogen duct kidney
constriction  Ang I
rate
ing oxygen demand. However, it is im-
portant to remember that clinical cases of ACE (lungs)
Retain water
shock usually do not fall neatly into one Push blood
back to
Ang I  Ang II
category and often straddle several cate- Maintain tissue
heart

perfusion
gories. The four categories described in
this article are listed in TABLE 1, along with Increase Adrenal
gland
venous return
an explanation of why each category
Release
meets the basic definition of shock. aldosterone

Increase
Compensation for Shock cardiac output
Retain Na in distal
Regardless of the cause, when tissues are tubules kidney
not properly supplied with oxygen, the
body attempts to remedy the situation by
initiating a series of neural and hormon-
ally mediated compensatory mecha- Increase blood
Improve oxygen
nisms. The end goal of these mechanisms volume
delivery to tissues
is to increase cardiac output and blood
vessel tone in an attempt to better supply
the cells with oxygen. These compensa- Figure 4. Compensatory mechanisms in response to shock. ACE = angiotensin-converting
Figure 4. Compensatory mechanisms in response to shock. ACE = angiotensin-converting enzyme,
tory mechanisms can be grouped into enzyme, Ang = angiotensin, JG = juxtaglomerular, [Na] = concentration of sodium, SNS =
Ang = angiotensin, JG = juxtaglomerular, [Na] = concentration of sodium, SNS = sympathetic nervous system.
sympathetic nervous system.
three separate categories: (1) effects ex-
erted within minutes (acute), (2) effects
exerted in 10 minutes to 1 hour (moderate), (3) and effects exerted are mediated by the sympathetic nervous system (SNS) and cat-
within 1 to 48 hours (chronic).1 In general, the body responds by in- echolamine release and take effect within 30 seconds to a few
creasing heart rate, increasing peripheral vascular tone, and attempt- minutes.1 As cardiac output decreases, impulse generation by the
ing to increase stroke volume, all in an effort to improve cardiac out- baroreceptors at the carotid sinus and aortic arch in the heart
put and keep perfusion to tissues intact. Stroke volume is improved decreases. Under normal conditions, baroreceptor impulses work
by increasing the amount of blood returned to the heart (e.g., venous to inhibit the vasoconstrictor center of the medulla and increase
return). One way to increase venous return is to shunt blood from stimulation of the vagal center in the brain, leading to vasodilation.
small (less important), peripheral vessels to the heart to supply the When the baroreceptor impulses are decreased, the vasomotor
myocardium, lungs, and brain. The kidneys provide a second way to center in the brain operates unchecked and SNS signals from the
improve venous return by retaining fluid to bolster the total blood brain increase. These increased SNS signals cause release of nor-
volume. FIGURE 4 summarizes these various compensatory mecha- epinephrine from the adrenal gland and the nerve endings them-
nisms; the following text discusses the compensation in more detail. selves. Norepinephrine binds to α-adrenergic receptors on blood
vessels to cause vasoconstriction and binds to β1-adrenergic re-
Acute Compensatory Mechanisms ceptors in the myocardium to cause an increase in heart rate and
Catecholamines contractility1,2 (FIGURE 4).
Acute compensatory effects are limited to those affecting heart A second important stimulus of catecholamine secretion is
rate and redistributing peripheral blood back to the heart. They hypoxemia.2 This can be true hypoxemia, represented by a global

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 Thomovsky E, et al. Shock pathophysiology. Compend Contin
Thomovsky E, et al. Shock pathophysiology.
Thomovsky Compend Contin
E, et al. Shock pathophysiology. Compend Contin
Educ Vet 2013;35(8).
Thomovsky E, et al.Vet
Shock pathophysiology. Compend Contin
Educ Vet 2013;35(8).
Educ 2013;35(8).
Shock Pathophysiology
Educ Vet 2013;35(8).

Blood vessel Interstitial Space

Blood vesselBlood vesselInterstitial Interstitial
Space Space
decrease in arterial oxygen content, or relative hypoxemia, caused Blood vessel Interstitial Space
by microcirculatory derangements that shunt blood away from
tissues. Chemoreceptors that sense the oxygen content of the blood
πi πi πi

No net fluid
are located in the carotid artery and aorta. Those in the carotid

Nomovement
πc πc

net fluid

No net fluid
πi

movement

movement
πc

fluid
artery sense decreased oxygen delivery to the brain and, therefore,

movement
πc
stimulate the vasomotor center to increase SNS stimulation regard-

No net
Pi Pi Pi
less of peripheral blood pressures.2 In the aorta, decreases in periph- Pc Pc Pc Pi
eral blood pressure are signaled by decreased baroreceptor stimu- Pc
lation and chemoreceptors are activated as a result of decreased
oxygen delivery.2 Both baroreceptor and chemoreceptor signals lead
A. Normal setting. No net fluid movement into either the interstitial or the vascular
A. Normal setting. No net fluid
A. Normal movement
setting. into movement
No net fluid either the interstitial
into eitherorthe
theinterstitial
vascular or the vascular
to increased SNS signals from the vasomotor center in the brain. compartment. There is a balance between oncotic pressure and hydrostatic pressure in each
compartment. There isNo
a balance between oncotic pressure and hydrostatic pressure in eachpressure in each
A. Normal setting.
compartment.net fluid movement
There intobetween
is a balance either the interstitial
oncotic or the
pressure vascular
and hydrostatic
compartment. The blood vessel wall permeability is normal (semipermeable). Oncotic pressure
compartment.
compartment. The blood
There is vessel
compartment. wall
a balance
The permeability
between
blood oncotic
vessel is pressure
wall normal (semipermeable).
and hydrostatic
permeability Oncotic in
pressure
is normal (semipermeable). pressure
each Oncotic pressure
works to hold fluid within a compartment; hydrostatic pressure works to push fluid out of a
works to hold fluid
compartment. Thewithin
blood avessel
compartment;
fluidwall ahydrostatic
permeability is pressure
normal works pressure
to push fluid
(semipermeable). outtoofpush
Oncotic a fluid out of a
pressure
Cortisol compartment.
compartment.
works to hold
works to holdcompartment.
within compartment; hydrostatic works
fluid within a compartment; hydrostatic pressure works to push fluid out of a
Cortisol is also rapidly mobilized in the acute stages of shock compartment.
(within minutes).1 Cortisol is released from the adrenal gland in Blood
Blood vesselBlood vesselInterstitial
vessel Space
Interstitial Space
Interstitial Space
response to corticotropin-releasing hormone (CRH) from the Blood vessel Interstitial Space
hypothalamus and also by stimulation via adrenocorticotropic
hormone.7 Stimuli such as pain and mental or physical stress can
lead to increases in CRH production. These stimuli are generated πi πi πi
πc πc πc πi
in or transmitted through the brain to the hypothalamus. Cortisol
πc
has many effects, and it is not completely understood which effect
Pc Pc Pc Pi Pi
is the most important in shock; however, stimulation of glycoge- Pi
Pc Pi
nolysis and mobilization of fat and protein stores for gluconeo-
genesis are often considered the most important.1 Release of glucose Net movement fluid into vessel
Net movement fluid into vesselfluid into vessel
Net movement
into the bloodstream provides a readily accessible energy source. Net movement fluid into vessel
We believe that the most important effects of this glucose surge Thomovsky E, et al. Shock pathophysiology. Compend Contin
B. Immediately after hypovolemia occurs (e.g., immediatelyThomovskypost-hemorrhage).
E, et al. Shock pathophysiology.
Net fluid movement Compend Contin
B. Immediately B. after hypovolemia Educ
occurs Vet
(e.g., immediately
2013;35(8):E1- post-hemorrhage). Net fluid movement
are to supply endothelial cells in the blood vessels with energy to Immediately after hypovolemia
into the vascular compartment. The hydrostatic pressure Educ
occurs (e.g.,
Vetwithin
immediately post-hemorrhage).
the blood vessel (Pc) is LESS than
2013;35(8):E1-
Net fluid movement
into
B.the vascularinto
Immediately compartment.
after vascularThe
the hypovolemia hydrostatic pressure
occurs (e.g.,
compartment. The within post-hemorrhage).
immediately
hydrostatic the bloodwithin
pressure vesselthe
(Pc)
Net isfluid
blood LESS than
movement
vessel (Pc) is LESS than
continue contraction, feed the myocardial cells to continue con- that in the interstitium (Pi) due to hypovolemia. Oncotic pressure (πc) is HIGHER in the blood vessel
that in the vascular
into interstitium (Pi)interstitium
due to The
thatcompartment.
in the hypovolemia.
(Pi) due toOncotic
hydrostatic pressurepressure
within
hypovolemia. (π c) blood
the
Oncotic is HIGHER
vessel(πin
pressure )the
(Pc) blood
is is LESSvessel
HIGHER than
in the blood vessel
than previously due to depletion of fluid. The blood vessel wall permeability is normal c
than
thatpreviously due to
in the interstitiumdepletion
(Pi) due oftofluid. The blood
hypovolemia. vessel
ofOncotic wall permeability
pressure is normal
(πc) is HIGHER in the blood vessel
traction, and allow brain cells to function in the short term. (semipermeable).
(semipermeable).
than previously due to depletion fluid. The blood vessel wall permeability is normal
than previously due to depletion of fluid. The blood vessel wall permeability is normal
(semipermeable).
(semipermeable).
Blood vessel Interstitial Space
Transcapillary Shifts Blood vessel Interstitial Space
A final mechanism that aids in the acute improvement in blood
volume is transcapillary shifting of fluid from the interstitium to
the vasculature. This happens at the capillary level, primarily in
cases of hypovolemic shock11 (FIGURE 5). When the pressure πi
πc πi
No net fluid

within the capillaries drops secondary to hypovolemia and vaso-

movement

πc No net fluid
movement
constrictive shunting of blood, Starling’s forces dictate that fluid
will move from an area of higher pressure (the interstitium) into Pc Pi
an area of lower pressure (the vessel). Fluid continues to move until Pc Pi
the dilution of proteins in the blood vessels (decreasing oncotic
pressure in the blood vessel) is balanced with the concentration of
proteins in the interstitium (increasing oncotic pressure). Addi- C. Cessation of transcapillary fluid shifting. After a period of net fluid movement into the vascular
compartment, the fluid
C. Cessation ofvolume in the interstitial
transcapillary spaceAfter
fluid shifting. is decreased
a period and thefluid
of net hydrostatic
movementpressure (Pi)vascular
into the
tionally, as fluid moves out of the interstitium into the vascular decreases. Dilution of intravascular
compartment, proteins
the fluid volume in theoccurs secondary
interstitial spacetoisfluid movement
decreased intohydrostatic
and the the blood pressure (Pi)
space, fluid volume and, therefore, pressure decrease in the inter- vessel, decreasing
decreases. capillary oncotic
Dilution of pressure proteins
intravascular (πc). Interstitial oncotic pressure
occurs secondary INCREASES
to fluid movement intoduethe
to blood
concentration
vessel,ofdecreasing
proteins incapillary
the interstitial
oncoticspace after (π
pressure fluid moves into the vessel. The blood vessel
c). Interstitial oncotic pressure INCREASES due to
stitium (decreasing hydrostatic pressure). wall permeability is normal (semipermeable). Fluid movement into the blood vessel stops.
concentration of proteins in the interstitial space after fluid moves into the vessel. The blood vessel
An additional step during transcapillary fluid shifting involves wall permeability is normal (semipermeable). Fluid movement into the blood vessel stops.
movement of proteins into the blood from storage sites in the mesen-
Figure 5. Transcapillary shifting of fluid during hypovolemic shock. Fluid movement
tery and liver.11 These proteins increase oncotic pressure in the blood is dictated by Starling’s law: Net fluid movement = [Pc – Pi] – δ[πc – πi] where
vessels to continue to help draw fluid from the interstitium into blood Pc= hydrostatic pressure in the capillary, Pi= hydrostatic pressure in the interstitium,
Figure 5. Transcapillary shifting of fluid during hypovolemic shock. Fluid movement is dictated
vessels and maintain the extra fluid within the blood vessels.11 πc= oncotic pressure in the capillary, πi = oncotic pressure in the interstitium, and
by Starling’s law: Net fluid movement = [Pc – Pi] – δ[πc – πi] where Pc= hydrostatic pressure in
the theFigure
δ= capillary, 5. Transcapillary
reflection coefficient.
Pi= hydrostatic
shifting
pressure
of fluid during
Theinreflection hypovolemic
coefficient
the interstitium,
shock. Fluid
essentially
πc= oncotic pressure in
movement
describes the
the capillary,
is dictated
πi
by Starling’s law: Net fluid movement = [Pc – Pi] – δ[πc – πi] where Pc= hydrostatic pressure in
=“leakiness” of the blood vessel wallsδ= and their ability to retain proteins, electrolytes
Moderate Compensatory Mechanisms oncotic pressure in the interstitium, and the reflection coefficient. The reflection coefficient
the capillary, Pi= hydrostatic pressure in the interstitium, πc= oncotic pressure in the capillary, πi
essentially describes the “leakiness” of the blood vessel walls and their ability to retain proteins,
and other substances
= oncotic pressure ininthe
theinterstitium,
lumen ofand theδ=capillary. In the
the reflection situations
coefficient. Thediscussed in
reflection coefficient
The next level of compensation starts within about 10 minutes to electrolytes and other substances in the lumen of the capillary. In the situations discussed in this
this figure,
figure, the describes
essentially
the reflectionreflection
coefficientcoefficient
consideredistoconsidered
theis“leakiness” be normal. to be normal.
of the blood vessel walls and their ability to retain proteins,
1 hour after the body enters the shock state. electrolytes and other substances in the lumen of the capillary. In the situations discussed in this
figure, the reflection coefficient is considered to be normal.

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 Shock Pathophysiology

Table 2. Physical Examination Findings at Each Stage of Shocka

Physical Examination Finding Compensated Shock Acute Decompensated Shock Late Decompensated Shock

Canine

Temperature ↓ (98°F–99°F) ↓↓ (96°F–98°F) ↓↓↓ (<96°F)

Heart rate ↑↑ (>180 bpm) ↑ (>150 bpm) Normal to ↓ (<140 bpm)

Respiratory rate ↑↑ (>50 bpm) ↑ (>50 bpm) ↑ to normal to agonal

Mentation QAR Obtunded Obtunded to stupor

Mucous membrane color Pale Pale Pale to muddy

Capillary refill time <1 sec <2 sec ≥2 sec

Mean arterial blood pressure ↓ to normal (70–80 mm Hg) ↓(50–70 mm Hg) ↓↓ (<60 mm Hg)

Feline

Temperature ↓ (<97°F) ↓↓ (<95°F) ↓↓↓ (<90°F)

Heart rate ↑↑↑ (>240) or ↓ (160–180 bpm) ↑↑ (>200 bpm) or↓↓ (120–140 bpm) ↑ (>180 bpm) or ↓↓↓ (<120 bpm)

Respiratory rate ↑↑↑ (>60 bpm, open-mouth breathing) ↑↑ (>60 bpm) ↑ rate to agonal

Mentation QAR Obtunded Obtunded to stupor

Mucous membranes Pale Pale to white Variable (pale to white to muddy)

Capillary refill time <1 sec <2 sec ≥2 sec

Systolic arterial blood pressure ↓ to normal (80–90 mm Hg) ↓(50–80 mm Hg) ↓↓ (<50 mm Hg)
a
Hypothetical values are given in parentheses to give the reader an idea of the approximate range of values found in each species at each stage of shock.
QAR = quiet, alert, responsive

Angiotensin II baroreceptors and stretch receptors (in the right and left atria).
Baroreceptors in the juxtaglomerular apparatus near the renal The atrial stretch receptors are active when there is a large volume
glomerulus sense decreased blood flow from decreased cardiac in the atria and work to inhibit vasopressin secretion; when the
output. This decreases impulse generation in the baroreceptors, atria are less full, more vasopressin is released because of lack of
which in turn leads to renin secretion. Renin causes conversion of inhibition. Even small alterations—a 1% change in osmolarity or
angiotensinogen to angiotensin I in the bloodstream. Angiotensin a 10% decrease in blood volume—lead to release of vasopressin.7
I is converted to angiotensin II in the lungs under the influence of Other stimuli, including nausea and hypoxia, also develop in patients
angiotensin-converting enzyme. Angiotensin II binds to angio- with shock and cause further release of vasopressin.7 Vasopressin
tensin receptors on the blood vessels and causes vasoconstriction. binds to V1 receptors on the arterioles, causing vasoconstriction.
The vasoconstriction not only improves blood vessel tone to main- As with angiotensin or norepinephrine, this improves vascular tone
tain perfusion to the tissues but also, more importantly, forces in an effort to maintain delivery of blood to tissues. Additionally,
blood from less important peripheral tissues (including the it increases return of blood from the peripheral tissues to the
splanchnic circulation) to the brain and heart to improve venous heart so that venous return and cardiac output are maintained.
return and cardiac output.2 Angiotensin II also retains water and
sodium in the kidneys to help maintain blood volume through renal Chronic Compensatory Mechanisms
artery vasoconstriction, which reduces filtration of blood through If the patient survives the shock situation, the final stages of com-
direct effects on the tubules that are not completely elucidated.1 pensation involve replacing the blood volume in the body. This
takes place from 1 to 48 hours after insult.
Vasopressin
Vasopressin is released from the posterior pituitary gland in response Aldosterone
to increased osmolarity (i.e., less water and more sodium in the At the same time that angiotensin II is exerting its effects on blood
blood that passes by the osmoreceptors in the hypothalamus) or vessels and the kidney, it is also stimulating the adrenal glands to
decreased effective circulating blood volume as sensed by the secrete aldosterone from the adrenal gland cortex.1 Aldosterone

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 Shock Pathophysiology

Table 3. Physical Examination Findings During Shock States

Physical
Examination
Finding Compensated Shock Acute Decompensated Shock Late Decompensated Shock
Canine
Rectal During vasoconstriction, peripheral vessels Vasoconstrictive shunting of blood away While vasoconstrictive shunting of blood is
temperature such as those in the GI tract are preferentially from the GI tract continues. Simultaneously, still in progress, the largest factor in the
constricted. Reduced blood flow to the colon the decreased cardiac output with decreased temperature is the minimal amount
leads to a decreased rectal temperature. worsening shock equates to less blood of blood flow being delivered to the colon.
being delivered to the colon (and therefore
a lower rectal temperature).
Heart rate Activation of β1-adrenergic receptors by As the myocardium receives less oxygen, the Continued reduced myocardial perfusion and
epinephrine and norepinephrine leads to heart rate starts to decrease despite continued oxygen delivery leads to decreasing ability of
tachycardia. stimulation by the β1-adrenergic receptors. the heart to contract and a reduced heart rate.
Respiratory Multifactorial. Pain and stress lead to As oxygen delivery decreases to the Continued reduced oxygen delivery to the
rate tachypnea. Respiratory rate also increases diaphragm and other muscles of diaphragm and other muscles of
concurrent with perceived oxygen debt in respiration, the respiratory rate decreases. respiration leads to worsening respiratory
the respiratory center in the brain. rate decline.
Mentation Brain cells receive enough oxygen to As the cells of the brain receive less Continued reduced oxygen delivery to the
function, but the patient is less responsive oxygen delivery, the patient’s mentation brain leads to worsening obtundation.
than normal. Pain also alters mentation. declines (obtundation).
Mucous Pallor occurs primarily because of Pallor continues because of vasoconstriction Pallor occurs largely because of reduced
membrane vasoconstriction and shunting of blood and shunting of blood along with reduced peripheral perfusion. Muddy mucous
color away from the periphery. Hyperemia ability to deliver blood to peripheral tissues. membrane color develops when waste
develops because of massive release of products of cellular metabolism diffuse
vasodilatory mediators such as nitric oxide into capillaries but are not removed from
(seen in cases of sepsis and SIRS) the region because of reduced perfusion.
Capillary refill Rapid refill caused by increased vascular Blood vessels start to become refractory to Blood vessels lose the ability to constrict
time tone (binding by epinephrine, norepinephrine, constriction because of reduced oxygen because of severely decreased oxygen
ANG II and vasopressin to receptors on delivery to endothelial cells. Vasodilatory delivery to those cells and the overwhelming
vascular endothelium). effectors such as nitric oxide start to influence of vasodilatory signals such as
overwhelm vasoconstrictors. nitric oxide.
Mean arterial The body is able to maintain near normal Gradual loss of vascular tone occurs Ability to vasoconstrict is lost because of
blood pressure, primarily because of vasocon- because of reduced oxygen delivery to the reduced oxygen delivery; reduced cardiac
pressure striction. vascular endothelium. output leads to reduced vascular volumes.
Feline
Temperature Same as canine.
Heart rate Cats rarely display tachycardia during shock. Cats in shock are often bradycardic and become more so over time. Cats in compensated
shock tend to have heart rates ≤160 bpm, and cats in decompensatory shock tend to have heart rates ≤100 bpm.
It is not completely understood why cats respond to shock with relative to absolute bradycardia without first having a discernible period of
tachycardia, despite having increases in SNS signals similar to dogs.
Respiratory Cats display profound tachypnea that can resemble respiratory distress. It is not completely understood why cats have such a dramatic
rate response compared with dogs. However, the lungs are considered the “shock” organ in cats and, as such, receive markedly decreased
perfusion during vasoconstrictive conditions, which may contribute to the extreme tachypnea and respiratory distress.
Mentation Same as canine.
Mucous It is often difficult to visualize color and perform a capillary refill time even in healthy cats. However, it is likely that they follow a similar
membranes/ pattern to dogs.
capillary refill
time
Mean arterial Same as canine.
blood pressure

SIRS = systemic inflammatory response syndrome; SNS = sympathetic nervous system; ANG II = angiotensin II

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 Shock Pathophysiology

increases sodium reabsorption in the distal

convoluted tubule of the kidney. Water Shock
follows the sodium and is reabsorbed
into the blood vessels, increasing blood
Opioid pain medications (if indicated)
volume. Whenever blood volume is in-
creased, there is improved venous return Cardiogenic
(and therefore cardiac output). Hypovolemic
Obstructive Distributive

Antidiuretic Hormone
Vasopressin has another effect in the body
as antidiuretic hormone (ADH). Vaso-

Vasodilatory component
pressin and ADH are the same hormone; Administer
proximal to
the two names reflect the two divergent obstruction
Positive inotropes
effects in the body. When produced,
(dobutamine)
ADH binds to V2 receptors in the col-
lecting ducts of the kidney.1 This induces Fluids
insertion of aquaporin channels into the
collecting ducts to allow reabsorption of Vasopressors (dopamine,
norepinephrine, vasopressin,
water from the ducts. ADH also stimulates Relieve epinephrine)
obstruction (if
thirst to increase the amount of water in the indicated) Treat
body and thereby improve blood volume underlying
cardiac
and venous return.
Patient stabilizes based disease (if
on vital statistics, present)
Clinical Signs Associated mentation, blood
With Shock pressure

Building on the basic physiology of the

shock response allows better understand- lize
Does not
ing of the clinical signs associated with stabilize
an animal presenting in shock. Patients
Further diagnostics
go through three stages of shock: com- (imaging, full
More fluids
pensatory, acute decompensatory, and blood work) Full PE – look
for ongoing
late decompensatory. Other terms for hemorrhage
these stages are compensatory reversible Positive inotropes Vasopressors
(dobutamine) – if (dopamine, vasopressin Check for
shock, uncompensated reversible shock, and norepinephrine) – if not hypoglycemia
not already in use
uncompensated irreversible shock. In the
3 already in use
compensated stage, by virtue of the vari-
ous physiologic mechanisms discussed Figure 2. Treatment of shock. PE = physical examination.
Figure 6. Treatment of shock. PE = physical examination
above, the patient is able to maintain
oxygen delivery to the tissues to preserve
normal cellular metabolism. In the acute stage of decompensation, compensated shock, the expected mucous membrane color is pale
the demand for oxygen is greater than the delivery despite the because of vasoconstrictive shunting of blood away from the mucous
action of the physiologic mechanisms; therefore, the cells are forced membranes. However, in some cases, the mucous membranes
to switch to anaerobic metabolism, which yields less energy. In the can appear hyperemic.9,10 Hyperemic mucous membranes may
later stages of decompensation, inappropriate oxygen delivery be seen in diseases in which vasodilation overwhelms the vaso-
continues and the cellular demand for oxygen is not met, causing constriction expected in compensated shock. Notable examples
further anaerobic metabolism and less available ATP to the cells. are septic shock and SIRS, in which vasodilatory mediators such
In veterinary medicine, determination of the patient’s stage of as nitric oxide and cytokines that directly dilate the blood vessels
shock is based largely on the physical examination findings for are produced, leading to vasodilation.9,10 Later, in decompensatory
that patient. See TABLE 2 for a summary of the physical examination shock, the pallor seen in SIRS and sepsis patients is caused by a
findings found at each stage of shock and TABLE 3 for the reasons lack of blood delivery to the mucous membranes, not vasocon-
each finding exists at that stage. strictive mechanisms.
The physical examination finding that has the most variability Cats may not display the classic sign of tachycardia seen in
in cases of shock is the mucous membrane color. Based purely on dogs. While there is no clear reason for this species difference,
the physiologic responses to which a patient is exposed during cats in shock that tend to display bradycardia (heart rate <140

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 Shock Pathophysiology

bpm) or relative bradycardia (heart rate <160 bpm) are often septic can obstruct blood vessels) and release cytokines that cause depres-
or have SIRS.9,10 sion of the myocardium but also, if untreated, prevent resolution
of the patient’s condition. Also complicating the situation is the
Treatment fact that improving macrovascular parameters such as heart rate
In veterinary medicine, treatment for shock should be aimed at or peripheral blood pressure does not necessarily mean that micro-
addressing the basic pathophysiologic mechanisms. Gauging a circulation (capillary perfusion) has been restored.4,8 However, at
response to treatment for patients in shock is based on normalizing this time, clinicians do not have a clinically dependable bedside
vital parameters and, often, peripheral blood pressure. There are diagnostic test or tool that allows assessment of the microcirculatory
very limited options available to clinicians to treat cases of shock response to resuscitation.
(FIGURE 6). In any treatment situation, continuous reassessment of the
Hypovolemic shock is primarily treated by large-volume fluid patient’s vital parameters and status to determine whether resus-
resuscitation. Crystalloid fluid doses for patients in shock are 90 citation efforts have been successful is most important. If the patient
mL/kg/h in dogs and 60 mL/kg/h in cats. It is recommended to does not seem to be improving as hoped, continue to administer
give one-quarter to one-third of the calculated fluid dose to the treatment as suggested by the patient’s condition, but reassess the
animal in a bolus as quickly as possible and then reassess the patient with a complete physical examination to look for indications
patient’s vital parameters. The fluid bolus can be repeated as of occult hemorrhage (e.g., into a body cavity or a fracture hema-
many times as necessary until the parameters have normalized toma) that would lead to ongoing signs of hypovolemic shock. It
or the hourly amount has been met. Further or additional steps is important to document that a refractory patient is not suffering
might include administration of boluses of colloids (typically 5 to from hypoglycemia caused by depleted liver stores occurring after
10 mL/kg repeated until the patient is stabilized or to a maximum exuberant cortisol release. Finally, especially in trauma patients,
dose of 20 mL/kg for colloids such as hetastarch). if the patient does not improve with resuscitation, imaging of
Obstructive shock is treated with fluids administered at shock body cavities is indicated to look further for blood loss or other
doses in a vascular location where the fluids will return to the abnormalities, such as pneumothorax, that might decrease venous
heart and not be trapped distal to the obstruction. For example, return to the heart and further the shock condition.
a patient with gastric dilatation-volvulus (GDV) should receive Shock is a complex interaction between the inciting event and
fluid in the cephalic veins, not the lateral saphenous veins. When the body’s compensatory mechanisms. In understanding basic
applicable, the clinician should also attempt to relieve the ob- pathophysiology, clinicians should be able to better recognize
struction (e.g., surgery to relieve GDV). patients in shock and to logically determine the best steps for
Cardiogenic shock does not involve decreased blood volume resuscitation of these patients.
and instead is a failure of the heart to effectively pump blood to
tissues. It is treated with positive inotropes (e.g., dobutamine) References
without fluid therapy. In some cases, drugs that cause vasodilation 1. Hall JE. Circulatory shock. In: Guyton and Hall Textbook of Medical Physiology. 12th
and reduce afterload, such as nitroprusside, are also used to improve edi. Philadelphia, PA: Saunders Elsevier; 2011:273-282.
cardiac output. It is important to limit or forgo fluid therapy in 2. Bonanno FG. Physiopathology of shock. J Emerg Trauma Shock 2011;4(2):222-232.
3. Brown SGA. The pathophysiology of shock in anaphylaxis. Immunol Allergy Clin
patients with cardiogenic shock because the heart may already be
North Am 2007;27:165-175.
fluid overloaded by shunting of blood to the heart caused by vaso- 4. Elbers PWG, Ince C. Bench-to-bedside review: mechanisms of critical illness—classifying
constriction during compensation. microcirculatory flow abnormalities in distributive shock. Crit Care 2006;10:221.
Distributive shock is the most difficult form of shock to treat 5. Ben-Shoshan M, Clarke AE. Anaphylaxis: past, present and future. Allergy 2010;66:1-14.
because it involves derangement of the microvasculature as well 6. Moranville MP, Mieure KD, Santayana EM. Evaluation and management of shock
states: hypovolemic, distributive and cardiogenic shock. J Pharm Pract 2011;24(1):44-60.
as the macrovasculature. These patients are treated with shock
7. Woolf PD. Endocrinology of shock. Ann Emerg Med 1986;15:1401-1405.
doses of fluids to improve hypovolemia resulting from increases in 8. Szopinski J, Kusza I, Semionow M. Microcirculatory responses to hypovolemic
vascular permeability and maldistribution of fluids into the dilated shock. J Trauma 2011;71(6):1779-1787.
vessels. Patients also require treatment with drugs to promote 9. Boag AK, Hughes D. Assessment and treatment of perfusion abnormalities in the
vasoconstriction, such as vasopressin, dopamine, epinephrine, or emergency patient. Vet Clin North Am Small Animal Pract 2005;35(2):319-342.
10. deLaForcade AM, Silverstein DC. Shock. In: Silverstein DC, Hopper K, eds. Small
norepinephrine and, in some cases, positive inotropes to improve
Animal Critical Care Medicine. St. Louis, MO: Saunders Elsevier; 2009:41-45.
myocardial depression (dobutamine). Finally, the underlying 11. Boulpaep EL. Integrated control of the cardiovascular system. In: Boron WF, Boulpaep
cause of the distributive shock must be addressed. Diseases leading EL, eds. Medical Physiology: a Cellular and Molecular Approach. Philadelphia, PA: Elsevier
to distributive shock may not only cause hypercoagulability (which Saunders; 2003:574-590.

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 Shock Pathophysiology

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1. Which of the following lists the correct variables for 6. Which disease entity would most likely cause cardiogenic
cardiac output? shock?
a. heart rate, preload, stroke volume, oxygen saturation a. hemoabdomen
b. preload, afterload, contractility, heart rate b. third-degree AV block

c. hemoglobin, afterload, arterial oxygen content, stroke c. pulmonary thromboembolism

volume d. dilated cardiomyopathy
d. stroke volume, arterial oxygen content, hemoglobin, 7. A dog with the following physical examination findings
heart rate would be classified in which stage of shock?
• Temperature: 94.5°F
2. Acute compensatory mechanisms that work to restore
• Heart rate: 120 bpm
perfusion to the tissues demonstrate their effects within
• Respiratory rate: 60 breaths/min
what time frame?
• Mentation: obtunded
a. days • Mucous membrane color: pale
b. minutes • Capillary refill time: >2 sec
• Mean arterial pressure: 50 mm Hg
c. hours
a. Compensated
d. months
b. Acute decompensated
3. Which of the following compensatory mechanisms does c. Acute compensated
not happen within the first 30 minutes after onset of shock? d. Late decompensated
a. release of aldosterone
8. Which of the following does not happen during distributive
b. increase in heart rate
shock?
c. increase in sympathetic tone a. decreased cardiac contractility
d. release of norepinephrine b. embolization of small blood vessels

4. Which of the following is a stimulus for the release of c. increased contractility

catecholamines? d. vasodilation
a. hypernatremia 9. __________is not generally associated with feline shock.
b. hypertension a. Tachycardia
c. hypoxemia b. Hypotension
d. hypercapnia c. Hypothermia
d. Tachypnea
5. Which of the following is not a stimulus for the release
of vasopressin? 10. _________ is a product of anaerobic cellular metabolism.
a. increased blood volume a. Vasopressin
b. hypoxia b. Glucose
c. nausea c. Oxygen
d. increased osmolarity d. Lactate

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