Shock

Question 1

Shock

Answer 1

• A condition of profound hemodynamic and metabolic disturbance characterized by failure of the circulatory system to maintain an appropriate blood supply to the microcirculation with consequent inadequate perfusion of vital organs
• The final common pathway for a number of potentially lethal clinical events: massive hemorrhage, extensive trauma and burns, massive MI, massive PE, bacterial sepsis
• Hypoperfusion and cellular hypoxia result in injury that is initially reversible but eventually irreversible that often proves fatal

Question 2

3 general categories of shock

Answer 2

• Cardiogenic shock
• Hypovolemic shock
• Septic shock

Question 3

Cardiogenic shock

Answer 3

Decreased cardiac output due to pump failure

Question 4

Hypovolemic shock

Answer 4

Decreased cardiac output due to loss of circulating volume

Question 5

Less common categories of shock

Answer 5

• Anaphylactic shock

- Neurogenic shock

Question 6

Anaphylactic shock

Answer 6

Widespread vasodilation and increased vascular permeability from IgE hypersensitivity reaction

Question 7

Neurogenic shock

Answer 7

Follow anesthetic accident, acute brain, or spinal cord injury, neural control of vasomotor tone is lost resulting in generalized vasodilation

Question 8

Systemic Inflammatory Response Syndrome (SIRS)

Answer 8

Exaggerated and systemic manifestation of a LOCAL inflammatory reaction, often fatal

Question 9

Systemic Inflammatory Response Syndrome (SIRS) - Diagnosis

Answer 9

2 or more signs of systemic inflammation (fever, tachycardia, tachypnea, leukocytosis or leukopenia) in the setting of a known cause of inflammation:

• T > 100.4 F (38 C) or 90 bpm
• RR > 20 breaths per min
• WBC > 12,000 or 10% immature WBCs is also significant

Question 10

Sepsis

Answer 10

SIRS with a culture-proven infection or obvious infection

Question 11

Septic Shock

Answer 11

Clinical SIRS severe enough to lead to hypotension and organ dysfunction

Question 12

Septic Shock - Epidemiology

Answer 12

• Mortality 20%
• 200,000 deaths per year in US
• # 1 cause of deaths in ICUs

Question 13

Septic Shock - Triggers

Answer 13

• Gram negative bacterial infections

- Gram positive bacterial and fungal infections

Question 14

Septic Shock - Inflammatory Mediators

Answer 14

TOLL-LIKE RECEPTORS (TLRs) on leukocytes
- Recognize microbial elements and trigger responses that start sepsis

TNF, IL-1, IFN-γ, IL-12, IL-18 + OTHERS are produced by inflammatory cells creating a PRO-INFLAMMATORY state

PROSTAGLANDINS and PAF
- Activate endothelial cells, causing adhesion molecule synthesis and pro-coagulant state

COMPLEMENT CASCADE

• Activated by microbial components
• Contributes to the hyperinflammatory states

Question 15

Septic Shock - Endothelial Cell Activation and Injury

Answer 15

Activation is by microbial components and inflammatory mediators

Question 16

Septic Shock - Endothelial Cell Activation and Injury - 3 major consequences of activation

Answer 16

THROMBOSIS - DIC (seen in up to 50% of patients with septic shock)

• Inflammatory mediators stimulate tissue factor and PAI-1 production
• Decreased production of tissue factor pathways inhibitor, thrombomodulin and protein C (anti-coagulant factors)
• Decreased blood flow produces stasis

INCREASED VASCULAR PERMEABILITY
- Causes 3rd spacing and edema which increases interstitial fluid pressure which impedes blood flow into the tissues = tissue hypoperfusion and stasis

VASODILATION
- Increased NO synthesis + vasoactive inflammatory mediators lead to vasodilation, hypotension and tissue hypoperfusion

Question 17

Septic Shock - Metabolic Abnormalities

Answer 17

Hyperglycemia and Insulin resistance

• Cytokines, stress-induced hormones and catecholamines drive GLUCONEOGENESIS
• Pro-inflammatory cytokines SUPPRESS INSULIN RELEASE and promote INSULIN-RESISTANCE
• RESULTING HYPERGLYCEMIA DECREASES NEUTROPHIL FUNCTION

Question 18

Septic Shock - Immune Suppression

Answer 18

• Hyperinflammatory state can activate counter-regulatory immunosuppressive mechanisms
• Whether immunosuppressive mediators are helpful or harmful in sepsis is UNCERTAIN

Question 19

Septic Shock - Organ Dysfunction

Answer 19

• Tissue hypoperfusion (resulting from hypotension, edema and small vessel thrombosis) starves organs of oxygen and nutrients
• Changes in cellular metabolism interfere with tissues utilizing nutrients
• Myocardial contractility is weakened by cytokines and secondary mediators decreasing cardiac output
• Decreased cardiac output, increased vascular permeability and endothelial injury can damage the lungs resulting in adult respiratory distress syndrome
• Other organs are affected by changes that take place in septic shock, particularly KIDNEYS, LUNGS, LIVER AND HEART

Question 20

Septic Shock - Stages

Answer 20

1. Nonprogressive phase
2. Progressive phase
3. Irreversible state

Question 21

Septic Shock - Stages - Nonprogressive phase

Answer 21

Reflex mechanisms compensate and tissue perfusion is maintained (SIRS)

Question 22

Septic Shock - Stages - Progressive stage

Answer 22

Tissue hypoperfusion ensues with worsening circulatory and metabolic imbalances including acidosis

Question 23

Septic Shock - Stages - Irreversible state

Answer 23

Such extensive cellular and tissue injury has occurred that even with infection control and hemodynamic correction, death is inevitable

Question 24

Septic Shock - Treatment

Answer 24

• Control infection with antibiotics
• Fluid resuscitation and vasopressor drugs to maintain systemic pressures
• Insulin therapy for hyperglycemia
• Corticosteroids at physiologic doses
• ANTI-INFLAMMATORY TREATMENTS TO CONTROL THE INFLAMMATORY RESPONSE HAVE NOT BEEN VERY SUCCESSFUL THUS FAR
• ACTIVATED PROTEIN C TO REDUCE COAGULATION AND INFLAMMATION IS STILL CONTROVERSIAL

Question 25

Septic Shock - Clinical outcome

Answer 25

• Initial threat of shock is from the underlying cause:MI, hemorrhage, sepsis, etc.
• Rapidly secondary complications of tissue hypoperfusion exacerbate the situation
• Prognosis varies with origin of shock, duration and underlying comorbidities of the patient