SAER 152: Pathophysiology of Shock

Question 1

List types of shock

Answer 1

circulatory shock:
- hypovolemia
- maldistributive
- cardiogenic
- obstructive
anemia
hypoxemia
impaired cellular oxygen utilization and energy production

Question 2

What is the broad definition of shock?

Answer 2

the VO2 exceeds DO2 and utilization –> leading to a cellular energy debt and measurable organ dysfunction

Question 3

DO2 is a function of ____ and ____

Answer 3

DO2 is a function of CO and CaO2

Question 4

CaO2 = ___ x ___ x ___ + ___

Answer 4

CaO2 = 1.34 x Hb x SO2 + 0.003 PaO2

Question 5

Fill in the blanks

Answer 5

Question 6

Explain how the delivery-independent Oxygen cosumption can be maintaned

Answer 6

1. DO2 in excess of VO2
2. Oxygen extraction only 25% under normal circumstances. Can be increased to 70-80% if DO2 is decreased

Question 7

When does oxygen consumption become delivery dependent?

Answer 7

When the DO2 drops to a point when oxygen extraction cannot be increased enough to compensate and VO2 will drop with further decline in DO2

Question 8

what are the intracellular consequences of decreased O2 delivery and consumption?

Answer 8

decreased DO2 and VO2 –> decreased phosphorylation in the mitochondria to produce ATP

–> cells respond by reducing metabolic activity

eventually switch to anaerobic metabolism –> lactate production

–> intracellular acidosis: denaturation of proteins, decreased enzyme function, disruption of transport mechanisms

inadequate cellular energy –> intracellular systems fail (ion pumps fail, oxygen free radical formation, loss of adenine nucleotides) –> tissue injury

ion pumps fail –> membrane integrity of cells fail –> fluid shifts into cells –> cellular edema

–> cellular necrosis or triggering of apoptosis

Question 9

What are the 3 stages of shock?

Answer 9

• compensated shock
• decompensated shock
• terminal/irreversible shock

Question 10

Explain the pathophysiology of compensated shock

Answer 10

the body is attempting to maintain core tissue/organ perfusion

• baroreceptors sense decreased vessel wall tension
• chemoreceptors sense hypoxia/hypercapnia/acidemia

► cathecholamine release

► tachycardia, increased cardiac contracility, peripheral vasoconstriction

► restores mean arterial perfusion pressure ► preserves perfusion of core organs

also: activation of RAAS system and increased release of vasopressin ► additional vasoconstriction + decreased urinary water loss
also: decrease in hydrostatic pressure (if applicable) ► water movement from itnerstitial into intravascular compartment

May happen at the expense of peripheral and splanchnic circulation ► hypoxic damage happens here already in compensated phase of shock

Question 11

Explain the pathophysiology of decompensated shock

Answer 11

compensatory mechanisms are overwhelmed/exhausted

► impaired core perfusion

• hypotension ► hypoperfusion ► hyperlactatemia ► metabolic (lactic) acidosis ► progressive catecholamine insensitivty

► vasodilation/ loss of vasomotor tone ► impaired venous return ► decrease in CO

► bradycardia ► decrease in CO

► irreversible/terminal shock

Question 12

List 5 groups of complications arising from shock

Answer 12

1. Systemic inflammatory response
2. Coagulopathy
3. Mitochondrial dysfunction
4. Microcirculatory dysfunction
5. Multiple organ dysfunction syndrome

Question 13

What are the causes for systemic inflammation in shock?

Answer 13

1. upregulation and release of inflammatory cytokines, e.g., IL-6, G-CSF

• IL-6 and G-CSF serve as chemotactic factors ► neutrophil infiltration into affected tissues ► diapedesis
• ► neutrophils release reactive oxygen and nitrogen species and proteolytic enzymes
• ► vasodilation, increased capillary permeability, dectruction of extracellular matrix
• ► tissue edema ► decreased O2 and metabolite exchange ► cellular dysfunction
• neutrophil plugging on endothelium ► vessel obstruction ► disruption of microcirculatory blood flow

2. activation of the complement system

• tissue injury ► release of split products, e.g., C3a, C5a (i.e., anaphylactoxins)
• lead to
• ► increased vascular permeability
• ► histamine and arachidonic acid product release
• ► cytokine production and release,
• ► promote aggregation and adherence of granulocytes to endothelium

increased activity of phospholipases A2 and C

• stimulates production of prostaglandins and leukotrienes
• ► further recruitment of inflamamtory cells
• ► alterations in vascular permeability
• ► impaired vasomotor tone
• ► enhanced platelet activity and aggregation

“shock gut”

• decreased intestinal perfusion ► increased intestinal permeability ► bacterial translocation

after reperfusion ► release of toxic metabolites and reactive oxygen species

• hypoxanthines accumulate during ischemia
• reperfusion ► O2 reintroduced ► formation of ROS
• lipid peroxidation, membrane disruption, DNA damage
• ► further cell damage ► necrosis and apoptosis

Question 14

Explain how shock leads to coagulopathy

Answer 14

shock ► systemic inflammation

• inflammatory cytokines (IL-1, IL-6, TNF-alpha, arachidonic acid metabolites) ► procoagulant
• increased expression of tissue factor on endothelium and monocytes
• consumption and downregulation of natural anticoagulants (protein C, antithrombin
• increased activity of Plasminogen-activator-inhibitor (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI)

► hypercoagulable state ► microthrombi

• arterial clots ► impairs tissue perfusion
• venous clots ► impairs venous return and oxygenation (if PTE)

►consumption of clotting factors + platelets ► hypocoagulable state

Question 15

Explain how shock causes mitochondrial damage

Answer 15

• inflammatory cytokines (e.g., TNF-alpha) ► uncoupling of oxidative phosphorylation, increased mitochondrial permeability and apoptosis
• increased production of reactive oxygen and nitrogen species and decreased ability to scavange free radicals
• reperfusion injury (increased free radicals)

Question 16

During shock, what leads to microvascular derangements, other than decreased perfusion?

Answer 16

• endothelial edema from ischemic injury ► increaed wall thickness decreases diameter
• increased permeability
• damage from inflammatory mediators ► inflammation ► endothelial activation ► leukocyte adhesion and capillary plugging
• arterial microthrombi ► impaired blood flow

Question 17

Explain how the gastrointestinal tract is compromised during shock

Answer 17

►splanchnic and periferal circulation is first ot be compromised during compensatory vasoconstriction to preserve perfusion of vital organs ► ischemic injury

►epithelial injury and loss of mucosal barrier ► bacterial translocation

► reperfusion injury ► shown to cause dysmotility

Question 18

Briefly describe the pathophysiology of ARDS

Answer 18

• ARDS involves inflammation-induced diffuse alveolar-capillary injury and subsequent severe accumulation of proteinaceous edema in the pulmonary interstitium and alveoli