2. shock
• tissue hypoperfusion that is insufficient to maintain normal aerobic
metabolism
• consists of inadequate tissue perfusion marked by decreased
delivery of required metabolic substrates and inadequate removal of
cellular waste products
• the resultant cellular injury is initially reversible; if the hypoperfusion is
severe enough and prolonged, the cellular injury becomes irriversible
• the clinical manifestations are the result of:
•stimulation of the sympathetic and neuro-endocrine stress responses
• inadequate oxygen delivery
• end-organ dysfunction
4. neuro-endocrine response to hemorrhage
• its goal is to maintain perfusion to the heart and brain , even at the expense of other organ systems
• mechanisms include:
• autonomic control of peripheral vascular tone and cardiac contractility
• hormonal response to stress and volume depletion
• local microcirculatory mechanisms that are organ specific and regulate regional blood flow
afferent signals
• loss of circulating blood volume
• pain, hypoxemia, hypercarbia, acidosis,
infection, changes in temperature,
emotional arousalm, hypoglycemia
• baroreceptors
• within the atria of the heart which efferent signals
are sensitive to changes in chambert- • cardio-vascular response
pressure and wall stretch • hormonal response
• aortic arch and carotid bodies • circulatory homeostasis
• chemoreceptors in the aorta and carotid • microcirculatory respons
bodies are sensitive to changes in O2
tension, H+ ion concentration, and carbon
dioxide (CO2) levels
• stimulation of the chemoreceptors
results in vasodilation of the
coronary arteries, slowing of the
heart rate, and vasoconstriction of
the splanchnic and skeletal
circulation
• a variety of protein and nonprotein
mediators are produced at the site of injury
as part of the inflammatory response, and
they act as afferent impulses to induce a
host response
5. cardio-vascular response
• hemorrhage results in diminished venous return to the heart and
decreased cardiac output
• stimulation of sympathetic fibers innervating the heart
leads to activation of beta1-adrenergic receptors that
increase heart rate and contractility
• sympathetic stimulation of the peripheral circulation via
the activation of alpha1-adrenergic receptors on arterioles
induces vasoconstriction and causes a compensatory
increase in systemic vascular resistance and blood pressure
• sympathetic stimulation also induces constriction of
venous vessels, decreasing the capacitance of the circulatory
system and accelerating blood return to the central
circulation
6. hormonal response
• shock hypothalamus (CRH) pituitary gland (ACTH) adrenal cortex (cortisol)
• cortisol stimulates gluconeogenesis and insulin resistance, resulting in hyperglycemia
• cortisol stimulates muscle cell protein breakdown and lipolysis to provide substrates
for hepatic gluconeogenesis
• cortisol causes retention of sodium and water by the nephrons of the kidneys
• renin-angiotensin system is activated in shock
• decreased renal artery perfusion, beta-adrenergic stimulation, and increased renal
tubular sodium concentration cause the release of renin from the juxtaglomerular cells
• decreased renal •release of renin • renin catalyzes the • angiotensin I has no significant functional
artery perfusion from the conversion of activity
• beta-adrenergic juxtaglomerular angiotensinogen • angiotensin II
stimulation cells (produced by the • a potent vasoconstrictor of both
• increased renal liver) to angiotensin splanchnic and peripheral vascular
tubular sodium I, which is then beds
concentration converted to • stimulates the secretion of
cause the release angiotensin II by aldosterone, ACTH, and antidiuretic
of renin from the angiotensin- hormone (ADH)
juxtaglomerular converting enzyme • aldosterone acts on the
cells (ACE) produced in nephron to promote
the lung reabsorption of sodium water.
• potassium and
hydrogen ions are lost
in the urine in exchange
for sodium.
7. • epinephrine
• hypovolemia • angiotensin II
• pain
• changes in circulating • hyperglycemia
blood volume sensed by
baroreceptors and left • pituitary gland releases increase the
atrial stretch receptors vasopressin or ADH release of ADH
• increased plasma
osmolality detected by
hypothalamic
osmoreceptors
• ADH acts:
• on the distal tubule and collecting duct of the nephron to
increase water permeability, decrease water and sodium
losses, and preserve intravascular volume
• as a potent mesenteric vasoconstrictor, shunting circulating
blood away from the splanchnic organs during hypovolemia
• this may contribute to intestinal ischemia and
predispose to intestinal mucosal barrier dysfunction in
shock states
• increases hepatic gluconeogenesis and increases hepatic
glycolysis
8. Microcirculation
• the microvascular bed is innervated by the sympathetic nervous system and has a profound effect on the larger
arterioles
• other vasoactive proteins including:
• following hemorrhage • vasopressin
larger arterioles • angiotensin II
vasoconstrict; small • endothelin-1
distal arterioles
vasodilate • also lead to vasoconstriction to limit
organ perfusion to organs such as skin,
skeletal muscle, kidneys, and the GI
tract to preserve perfusion of the
myocardium and CNS
• flow in the capillary bed often is heterogeneous
in shock states, which likely is secondary to
multiple local mechanisms, including endothelial
cell swelling, dysfunction, and activation marked
by the recruitment of leukocytes
• failure of the integrity of • decreased capillary hydrostatic
the endothelium of the pressure secondary to changes in
microcirculation and blood flow and increased cellular
development of capillary uptake of fluid
leak, intracellular swelling,
and the development of
an extracellular fluid
deficit • intracellular swelling is multifactorial, but
dysfunction of energy-dependent mechanisms,
such as active transport by the sodium-potassium
pump contributes to loss of membrane integrity.
9. metabolic effects
• cellular metabolism is based primarily on the hydrolysis of adenosine triphosphate (ATP)
• majority of ATP is generated in our bodies through aerobic metabolism in the process of
oxidative phosphorylation in the mitochondria
• dependent on the availability of O2 as a final electron acceptor in the electron
transport chain
• when oxidative phosphorylation is insufficient, the
cells shift to anaerobic metabolism and glycolysis to
• O2 tension within a cell decreases, generate ATP
there is a decrease in oxidative • this occurs via the breakdown of cellular
phosphorylation, and the glycogen stores to pyruvate
generation of ATP slows
• under hypoxic conditions in anaerobic metabolism,
pyruvate is converted into lactate, leading to an
intracellular metabolic acidosis
• depletion of ATP potentially
influences all ATP-dependent
cellular processes:
• decreased intracellular pH also influences vital cellular functions such as:
• maintenance of cellular
• normal enzyme activity
membrane potential
• cell membrane ion exchange
• synthesis of enzymes and
• cellular metabolic signaling
proteins
• acidosis leads to changes in calcium metabolism and calcium
• cell signaling
signaling
• DNA repair mechanisms
10. immune and inflammatory responses
• a well regulated complex set of interactions between
circulating soluble factors and cells that can arise in
response to trauma, infection, ischemia, toxic, or
autoimmune stimuli
• direct tissue injury or infection
• activation of the active inflammatory • intracellular products from damaged and • pattern recognition receptors (PRRs) - cell surface
and immune responses by the release of injured cells can have paracrine and • Toll-like receptors (TLRs)
bioactive peptides by neurons in endocrine-like effects on distant tissues to • receptor for advanced glycation end
response to pain and the release of activate the inflammatory and immune products
intracellular molecules by broken responses – DANGER SIGNALING
cells, such as heat shock HYPOTHESIS • initiation of the repair process and the
proteins, mitochondrial • endogenous molecules (damage mobilization of antimicrobial defenses at the
peptides, heparan sulfate, high mobility associated molecular patterns site of tissue disruption
group box 1, and RNA {DAMP}) are capable of signaling • leads to intracellular signaling and release of
the presence of danger to cellular products including cytokines
surrounding cells and tissues
• DAMP:
• tissue-based macrophages or mast cells act as
• Hyaluronan oligomers
sentinel responders, releasing histamines,
• Heparan sulfate
eicosanoids, tryptases, and cytokines
• Extra domain A of
fibronectin
• Heat shock proteins 60,
70,
• Gp96
•Surfactant Protein A -
Defensin 2
• Fibrinogen
• Biglycan
• High mobility group box 1
• Uric acid
• Interleukin-1 S-100s
Nucleolin
11.
12. Hypovolemic/Hemorrhagic Shock
• most common cause of shock in the surgical or
trauma patient is loss of circulating volume from
hemorrhage
• acute blood loss
• decreased baroreceptor • decreased inhibition of
stimulation from stretch vasoconstrictor centers in the brain
receptors in the large arteries stem, increased chemoreceptor
stimulation of vasomotor centers,
and diminished output from atrial • increase vasoconstriction
stretch receptors and peripheral arterial
resistance
• epinephrine and norepinephrine
• induces sympathetic stimulation
release, activation of the renin-
angiotensin cascade, and increased
vasopressin release
13. Classification of Hemorrhage
Class
Parameter I II III IV
Blood loss (mL) <750 750–1500 1500–2000 >2000
Blood loss (%) <15 15–30 30–40 >40
Heart rate (bpm) <100 >100 >120 >140
Blood pressure Normal Orthostatic Hypotension Severe
hypotension
CNS symptoms Normal anxious confused obtunded,
mild tachycardia hypotension, immediately life
tachypnea marked threatening, and
tachycardia [i.e., generally
pulse greater requires
than 110 to 120 operative
beats per control of
minute (bpm)] bleeding
14. • the appropriate priorities in patients with hemorrhagic shock are:
• secure the airway
• control the source of blood loss
• IV volume resuscitation
• patients who fail to respond to initial resuscitative efforts should be assumed to have ongoing active hemorrhage from large
vessels and require prompt operative intervention
• diagnostic and therapeutic laparotomy or thoracotomy
• patients who respond to initial resuscitative effort but then deteriorate hemodynamically frequently have injuries that require
operative intervention
• patients who fail to respond to resuscitative efforts despite adequate control of ongoing hemorrhage
• have ongoing fluid requirements despite adequate control of hemorrhage
• have persistent hypotension despite restoration of intravascular volume necessitating vasopressor support
• exhibit a futile cycle of uncorrectable hypothermia, hypoperfusion, acidosis, and coagulopathy that cannot be interrupted
despite maximum therapy
• these patients have deteriorated to decompensated or irreversible shock with peripheral vasodilation and resistance to
vasopressor infusion
• mortality is inevitable once the patient manifests shock in its terminal stages
• transfusion of packed red blood cells and other blood products is essential in the treatment of patients in hemorrhagic shock
• current recommendations in stable ICU patients aim for a target hemoglobin of 7 to 9 g/dL
• fresh frozen plasma (FFP) should also be transfused in patients with massive bleeding or bleeding with increases in
prothrombin or activated partial thromboplastin times 1.5 times greater than control
• additional resuscitative adjuncts in patients with hemorrhagic shock include minimization of heat loss and maintaining
normothermia
• development of hypothermia in the bleeding patient is associated with acidosis, hypotension, and coagulopathy
• hypothermia in bleeding trauma patients is an independent risk factor for bleeding and death
15. Septic Shock (Vasodilatory Shock)
• vasodilatory shock is the result of dysfunction of the endothelium and vasculature secondary to circulating
inflammatory mediators and cells or as a response to prolonged and severe hypoperfusion
• hypotension results from failure of the vascular smooth muscle to constrict appropriately
• characterized by peripheral vasodilation with resultant hypotension and resistance to treatment with
vasopressors
• the most frequently encountered form of vasodilatory shock is septic shock
• other causes include:
• hypoxic lactic acidosis
• carbon monoxide poisoning
• decompensated and irreversible hemorrhagic shock
• terminal cardiogenic shock
• postcardiotomy shock
• vasodilatory shock seems to represent the final common pathway for profound and prolonged
shock of any etiology
• in addition to fever, tachycardia, and tachypnea, signs of hypoperfusion such as confusion, malaise, oliguria, or
hypotension may be present
• these should prompt an aggressive search for infection, including a thorough physical examination,
inspection of all wounds, evaluation of intravascular catheters or other foreign bodies, obtaining
appropriate cultures, and adjunctive imaging studies, as needed
16. • evaluation of the patient in septic shock begins with an assessment of the adequacy of their airway and
ventilation
• severely obtunded patients and patients whose work of breathing is excessive require intubation and
ventilation to prevent respiratory collapse
• vasodilation and decrease in total peripheral resistance may produce hypotension
• fluid resuscitation and restoration of circulatory volume with balanced salt solutions is essential
• empiric antibiotics must be chosen carefully based on the most likely pathogens (gram-negative rods, gram-
positive cocci, and anaerobes) because the portal of entry of the offending organism and its identity may not be
evident until culture data return or imaging studies are completed
• knowledge of the bacteriologic profile of infections in an individual unit can be obtained from most
hospital infection control departments and will suggest potential responsible organisms
• antibiotics should be tailored to cover the responsible organisms once culture data are available, and if
appropriate, the spectrum of coverage narrowed
• after first-line therapy of the septic patient with antibiotics, IV fluids, and intubation if necessary, vasopressors
may be necessary to treat patients with septic shock
• catecholamines are the vasopressors used most often
• hyperglycemia and insulin resistance are typical in critically ill and septic patients, including patients without
underlying diabetes mellitus
