P.20 HEMODYNAMIC DISORDERS, THROMBOEMBOLIC 4.

Anaphylactic shock
DISEASE, AND SHOCK (PART 6)  Severe allergic reaction: IgE-mediated type I hypersensitivity
Dr. Espiritu | September 11, 2018 reaction
 Cardiac output and arterial pressure are drastically decreased
o Release of histamine → vasodilation → increased vascular
OUTLINE
I. Shock capacity and vascular permeability
o Arterial vasodilation → decreased arterial pressure

I. SHOCK 5. Shock associated with systemic inflammation

 Systemic hypotension owing to the reduction of cardiac  Inflammatory mediators → arterial vasodilation, vascular
output or reduction of the effective circulating blood volume leakage, venous blood pooling → tissue hypoperfusion,
 It complicates and becomes the final common pathway for cellular hypoxia, metabolic derangements → organ
many lethal clinical events such as dysfunction → organ failure → death
o Hemorrhage  Clinical findings: Systemic Inflammatory Response Syndrome
o Extensive trauma or burns (SIRS)
o Myocardial infarction  May be non-microbial or microbial
o Pulmonary embolism
o Microbial sepsis a. Non-microbial
 Main consequences  Burns
o Impaired tissue perfusion  Trauma
o Tissue (cellular) hypoxia  Pancreatitis
 Initial phase: potentially reversible
 Prolonged: irreversible tissue injury, often fatal b. Microbial (Septic shock)
 Cause: gram (+) bacteria > gram (-) bacteria > fungi
CATEGORIES OF SHOCK o Gram-positive bacteria: endotoxin-like substance
o Gram-negative bacteria: endotoxin
o Fungi: endotoxin-like substance
 Old synonym: endotoxic shock
o No longer appropriate
 Superantigens (toxic shock syndrome) have similar
pathogenesis and manifestations with septic shock
 Pathogenesis:

1. Cardiogenic shock
 Results from low cardiac output due to myocardial pump
failure
 Caused by:
o Intrinsic myocardial damage (infarction)
o Ventricular arrhythmias
o Extrinsic compression (cardiac tamponade)
o Outflow obstruction (pulmonary embolism)

2. Hypovolemic shock
 Results from low cardiac output due to low blood volume
 Caused by:
o Massive haemorrhage
o Fluid loss from severe burns (3rd space losses)

3. Neurogenic shock
 Brought about by loss of vasomotor tone leading to general o Inflammatory and counter-inflammatory
vasodilation responses
 Occurs in the setting of an anesthetic accident or a spinal cord  Presence of the organism is recognized
injury  Immune cells produce TNF, IL-1, IFN-γ, IL-12, IL-
 Caused by: 18, and other inflammatory mediators
o General anesthesia  Endothelial cells are induced to upregulate adhesion
 Depresses vasomotor area molecules and produce cytokines and chemokines
o Spinal anesthesia  Activation of complement cascade
 Blockage of sympathetic nervous outflow  Anaphylotoxins (C3a, C5a)
o Brain damage  Chemotactic fragments (C5a)
 Vasomotor paralysis  Opsonins (C3b)
 E.g., concussion, contusion, brain ischemia  Activation of coagulation cascade

SYSPATH | 1 of 3 MODGIL
  Hyperinflammatory state induces counter-
inflammatory responses
 Anti-inflammatory cytokines (TH2 cells)
 Anti-inflammatory mediators: soluble TNF
receptor, IL-1 receptor antagonist, IL-10
 Lymphocyte apoptosis
 Cellular anergy
o Endothelial activation and injury
 Increased permeability → widespread vascular
leakage → tissue edema
 Production of NO, C3a, C5a, and PAF → vasodilation
→ systemic hypotension
o Induction of a procoagulant state
 Complication: DIC
 Normal endothelial cells: anticoagulant
 Activated endothelial cells: procoagulant
 ↑ tissue factor, plasminogen activator inhibitor-
1 
 ↓ tissue factor pathway inhibitor,
thrombomodulin, protein C, fibrinolysis
 Vascular leak and tissue edema → decreased blood
flow (stasis) → accumulation of coagulant factors →
thrombosis → DIC → severe: consumption of
coagulation factors and platelets → haemorrhage
o Metabolic abnormalities
 Suppression of insulin release
 due to pro-inflammatory cytokines
 Insulin resistance
 due to impaired surface expression of GLUT4
 Hyperglycemia
 due to induced gluconeogenesis by TNF, IL-1,
and stress-induced hormones
 results in decreased neutrophil function and
increased adhesion molecules on endothelial
cells
 Glucocorticoid surge → adrenal insufficiency →
glucocorticoid deficit
 Caused by depressed synthesis by intact
adrenals or due to adrenal necrosis
(Waterhouse Friderichsen syndrome)
o Organ dysfunction
 Systemic hypotension + interstitial edema +
thrombosis → hypoperfusion → hypoxia
 ↑ cytokines and secondary mediators →
↓ myocardial contractility, ↓ cardiac output,
↑ vascular permeability, ↑ endothelial injury →
ARDS
 Multiple organ failure: kidneys, liver, lungs, heart →
death
SYSPATH | 2 of 3
STAGES OF SHOCK
1. Non-progressive phase
 Initial reversible phase
 Activation of reflex compensatory mechanisms
o Neurohumoral mechanisms help maintain cardiac output
and blood pressure
 Baroreceptor reflexes
 Catecholamine release
 Activation of renin-angiotensin axis
 ADH release
 Generalized sympathetic stimulation
 Net effect
o Tachycardia
o Peripheral vasoconstriction (to increase pressure)
 Cold, pale skin
o Renal conservation of fluid
 Oliguria, anuria
Coronary and cerebral vessels are less sensitive to
sympathetic response
o Relatively normal caliber of vessels → blood flow →
oxygen delivery
 Vital organ perfusion is maintained
2. Progressive phase
 Occurs if underlying causes are not corrected
 Widespread tissue hypoxia
 Persistent oxygen deficit: anaerobic glycolysis replaces
aerobic respiration → lactic acidosis → low tissue pH
o Blunted vasomotor response
o Arteriolar dilation
o Blood pooling in the microcirculation
 Worsened cardiac output
 Anoxic injury to endothelial cells
 DIC
 Vital organs begin to fail
 Clinically: decreased urine output, altered mental state
3. Irreversible phase
 Widespread cell injury
o Lysosomal enzyme leakage
 Further aggravates the state of shock
 Bacterimic or endotoxic shock from ischemic bowel (release
of intestinal flora)
 Anuria due to acute tubular necrosis (ATN) or acute kidney
injury (AKI) and renal failure
 Loss of myocardial contractility due to synthesis of NO
MODGIL
MORPHOLOGY OF SHOCK
 Tissues may revert to normal except for neurons and
myocytes
1. Cardiogenic or hypovolemic shock
o Hypoxic injury
o Manifests in any tissue
a. Adrenals: cortical cell lipid depletion
 Seen in all forms of stress
 Not adrenal exhaustion
 Activation of vacuolated cells → utilization of stored
lipids for steroid synthesis
b. Kidneys: ATN or AKI
c. Lungs: resistant to hypoxic injury
d. Heart: widespread coagulation necrosis
e. Brain: ischemic encephalopathy
f. Gastrointestinal tract: hemorrhagic necrosis
2. Septic shock and trauma
a. Lungs: diffuse alveolar damage
b. Brain, heart, lungs, kidneys, adrenals, GIT: DIC

CLINICAL MANIFESTATIONS
 Depends on precipitating insult
1. Cardiogenic and hypovolemic shock
o Hypotension
o Weak and rapid pulse
o Cold, clammy, cyanotic skin
2. Septic shock
o Initially, warm and flushed skin (peripheral vasodilation)

THREAT TO LIFE
 Stems from the underlying condition
 Shock is exacerbated by electrolyte imbalance and metabolic
acidosis
 Survival of the initial complications does not spare one from a
second phase
o Renal insufficiency
o Severe fluid and electrolyte imbalances
 All patients in shock have an overlying threat to their lives
 Address the underlying conditions and the precipitated
complications

PROGNOSIS
 Varies with the origin and duration of the shock
 >90% of young healthy patients with hypovolemic shock
survive with appropriate management
 Septic shock or cardiogenic shock with myocardial infarction
are associated with worse mortality rates (up to 20%) even
with appropriate management

References: Dr. Espiritu’s lecture

Robbins and Cotran Pathologic Basis of Disease, 9th Ed., Kumar,
Abbas, & Aster

END

SYSPATH | 3 of 3 MODGIL