Pathophysiology of circulatory
shock
Shock - definition
 Severe tissue hypoperfusion resulting in low supply of
oxygen to the organs
 Systemic hypotension (of various causes) is present
 P = Q  R
 Q ~ CO = SV  f
 CO depends on
a) cardiac function
b) venous return (→preload)
• R – systemic resistance (mostly arterioles) - afterload
Cardiac function and venous function
 aa
Phases of shock
 Compensation of initiating cause
 Decompensation
 Refractory shock
Compensatory mechanisms and their limits
 Activation of sympathetic nervous system
(tens of seconds)
 Activation of RAAS (cca 1 hour)
 Vasoconstriction (if possible) – but it leads
into lower blood supply
 Vasodilatation in some tissues (esp.
myocardium)
 Positively inotropic effect of SNS (if
possible) – but at cost of higher metabolic
requirements of the heart
 Increased heart rate – but CO decreases in
high HR (>150 bpm)
 Keeping circulating volume by lower diuresis
– but at cost of acute renal failure
 Shift to anaerobic metabolism – but at cost
of ↓ ATP a ↑ lactate (acidosis)
 Shift of saturation curve of hemoglobin to
right (↑2,3-DPG)
 Hyperglycemia – but there is decreased
utilization of Glc in the periphery
Heart rate [min-1]
Cardiacoutput[dm3.min-1]
Decompensated shock
 ↓ BP
 ↓ diuresis
 Brain hypoperfusion – involvment of mental functions
 Acrocyanosis
 Tachypnoe
Shock at cellular level
 Mitochondrial dysfunction (result of
hypoxia) – lower production of ATP
 ↑ ROS production by dysfunctional
mitochondria
 Failure of ion pumps (e.g. Na/K ATP-ase
→↑intracelular Ca2+)
 Activation of Ca2+ -dependent proteases
 Lysosomal abnormalities – release of
lysosomal proteases
 ↓ intracelular pH, ↑ lactate
◦ promote hyperpolarization of muscle cells by
opening K+ channels → ↓Ca2+ entry →
↓smooth muscle cell and cardiomyocyte
contraction
Refractory shock
 Vicious circles
1)Vasodilatation ↔ hypoperfusion
◦ Endothelial cells contain two isoforms of nitric oxid synthase – constitutive
(eNOS) and inducible (iNOS)
◦ In lasting hypoxia of endothelial cells there is increased iNOS activity
(primarily physiological mechanism)
◦ ↑NO increases vasodilation and hypoperfusion
2) Myocardial hypoxia ↔ lower contractility
◦ Lower myocardial perfusion leads into ↓CO, which further reduces
coronary flow
◦ Myocardium does not benefit from the shift of Hb saturation curve –
efficiency of O2 extraction is already at its maximum
3) Brain hypoperfusion ↔ ↓SNS activity
◦ Lower perfusion of vasomotor centre leads first into SNS hyperactivity,
which is then followed by its supression
◦ That leads into ↓brain perfusion
Other vicious circles in refractory shock
* SIRS
* DIC
Forms of shock
a) Hypovolemic (“cold and dry“) shock – low circulating
volume, low preload
b) Distributive (“warm“) shock – low resistance, low
afterload, CO might be increased
c) Cardiogennic (“wet“) shock – low CO in bad cardiac
function, fluid congestion
d) Obstructive shock – low preload of one ventricle in
normovolemia and subsequent lowering of CO +
congestion – pathophysiology similar to cardiogennic
shock
Cardiac and venous function in shock
 Hypovolemic shock:
compensation by
the vasoconstriction
and cardiac
mechanisms
 Distributive shock:
compensation by
cardiac mechanisms
(vasoconstriction is
usually impossible)
 Cardiogennic (and
obstructive) shock:
compensation by
vasoconstriction
Q [dm3.min-1]
P [mmHg] in right atrium
Hypovolemic shock - causes
 Acute bleeding
 Burns, trauma
 Rapid development of ascites
 Acute pancreatitis
 Severe dehydratation
◦ Vomiting, diarrhoea
◦ Excessive diuresis (e.g. in diabetes insipidus)
Distributive shock - causes
 Anafylactic shock
 Anafylactoid shock
◦ Mediators of mast cells, but without IgE
◦ E.g. snake venoms, radiocontrasts
 Septic shock
◦ Role of bacterial lipopolysaccharides
◦ Bacterial toxins
◦ IL-1,TNF-α – stimulate synthesis of PGE2 and NO
 Neurogennic shock
◦ Vasodilatation as a result of vasomotoric centre (or its
efferent pahways) impairment
Cardiogennic shock - causes
 Myocardial infarction
 Arrhythmias
 Valvular disease (e.g. rupture of papillary muscles)
 Decompensation of heart failure in dilated/restrictive
cardiomyopathy, amyloidosis
 Overload by catecholamines (“tako-tsubo cardiomyopathy“ –
apical akinesia + basal hyperkinesia)
 Rupture of ventricular septum
 Obstructive shock – e.g. cardiac tamponade, massive
pulmonary embolism, aortic dissection
Organ complications in shock
 Lungs
◦ ARDS
 Liver
◦ necrosis of hepatocytes
 GIT
◦ stress ulcer
◦ Damage of intestinal mucosa by ischemic necrosis →
sepsis
 Kidneys
◦ Acute renal failure in vasoconstriction of a. afferens
◦ Acute tubular necrosis during ischemia
Disseminated intravascular coagulopathy
(DIC)
 Systemic exposure to
thrombin
 Consequence of the vessel
wall damage
 Moreover, slower blood flow
contributes to the extent of
coagulation reactions
 Two phases:
1) Formation of microtrombi
(with local ischemia)
2) Bleeding as a result of
consummation of
coagulation factors
 DIC is especially frequent in
septic shock
Systemic Inflammatory Response Syndrome(SIRS)
 Systemic activation of immune mechanisms
 Causes:
◦ infections (sepsis)
◦ Shock caused by non-infectious causes (diffuse
tissue damage in hypoxia)
◦ Non-compatible blood transfusions
◦ Radiation syndrome (esp. GIT form)
Adult Respiratory Distress Syndrome (ARDS –
„shock lung“)
 Result of lung inflammation in
SIRS, pulmonary infections,
aspiration of gastric juice,
drowning
 Exsudative phase (hours):
cytokine release, leukocyte
infiltration, pulmonary edema,
destruction of type I
pneumocytes
 Proliferative phase: fibrosis, ↑
dead space, proliferation of
type II pneumocytes
 Reparative phase: ↓
inflammation, ↓ edema,
continuing fibrosis, in most
cases permanent restrictive
diseases
Multiorgan dysfunction syndrome
(MODS)
 Failure of more organs at once (lungs,
liver, GIT, kidneys, brain, heart)
 It can develop after initial insult (days or
weeks)
 Hypermetabolism, catabolic stress
 Can both preceed or result from SIRS
 (primary vs. secondary MODS)
General principles of treatment
 Treatment of underlying cause
 Positively inotropic drugs, vasopressors (e.g.
catecholamines – but: they can worsen the situation
in obstructive shock)
 Colloid solutions, crystaloid solutions (but: there is
a risk of edema in cardiogennic shock)
 O2
 i.v. corticoids (anafylaxis, SIRS?)
 ATB (septic shock)
 Mechanic circulation support (cardiogennic shock)
 Anti-shock position