Pathophysiology
II-23. Progression of circulatory shock
循環性ショックの進行
Progression of Circulatory Shock
- Transition compensated → progressive → irreversible is driven by positive-feedback vicious cycles and metabolic derangement
Exhaustion of Negative Feedback (entry to progressive stage)
- ↓renal medullary osmotic gradient (↓urine concentration)
- ADH depletion, catecholamine depletion + adrenoceptor desensitization
- Vasodilator mediators, metabolites and toxins from tissues
- Auto-infusion failure (reduced vessel resistance, ↑capillary hydrostatic pressure, ↓colloid osmotic pressure)
Positive-Feedback Vicious Cycles
- ↓coronary perfusion → ↓CO → ↓arterial pressure → further ↓coronary flow
- ↓brain perfusion → compromised SYM outflow from the vasomotor center
- Tissue hypoxia → vasodilator mediators/toxins from damaged cells → venous pooling (blood not returned to circulation)
- Vessel-wall hypoxia → no ATP → vasodilation, with ↑permeability → edema + electrolyte loss → ↓blood volume/venous return
Metabolic Changes
- Metabolic acidosis: tissue hypoxia → lactic acid (anaerobic metabolism), and tissue hypercapnia → carbonic acid (insufficient CO₂ removal)
- Mitochondrial depression: ↓ATP → ↓Na⁺/K⁺ ATPase → cell swelling → lysosome destabilization → cell necrosis
Irreversibility
- Dominance of positive feedback (“vicious circles”) → death despite external intervention → MOF/MODS
- The CNS ischemic (Cushing) response at ~50 mmHg gives a transient BP plateau but cannot reverse the decline
- Using BP alone is misleading (falls later than CO) — monitor additional perfusion parameters
一問一答
▶How does tissue hypoxia cause venous pooling in progressive shock?
Hypoxia releases vasodilator mediators/toxins from damaged cells, causing venous pooling so blood is not returned to the circulation.
▶How does reduced brain perfusion worsen shock?
It compromises sympathetic outflow from the vasomotor center, further reducing vascular tone and CO.
▶What drives the transition from compensated to progressive to irreversible shock?
Positive-feedback vicious cycles and metabolic derangement.
▶Describe the coronary vicious cycle in progressive shock.
↓Coronary perfusion → ↓CO → ↓arterial pressure → further ↓coronary flow.
▶What signs of negative-feedback exhaustion mark entry to the progressive stage?
Decreased renal medullary osmotic gradient, ADH and catecholamine depletion with adrenoceptor desensitization, vasodilator mediators/toxins from tissues, and auto-infusion failure.
▶How does vessel-wall hypoxia reduce blood volume?
No ATP → vasodilation with increased permeability → edema + electrolyte loss → ↓blood volume and venous return.
▶What are the two sources of metabolic acidosis in progressive shock?
Tissue hypoxia → lactic acid (anaerobic metabolism), and tissue hypercapnia → carbonic acid (insufficient CO₂ removal).
▶How does mitochondrial depression lead to cell necrosis in shock?
↓ATP → ↓Na⁺/K⁺ ATPase → cell swelling → lysosome destabilization → cell necrosis.
▶What characterizes the irreversible stage of circulatory shock?
Dominance of positive-feedback vicious circles → death despite external intervention → MOF/MODS.
▶Why can the CNS ischemic (Cushing) response not reverse shock decline?
At ~50 mmHg it produces only a transient BP plateau and cannot overcome the dominant positive-feedback cycles.
▶Why is blood pressure alone misleading when monitoring shock progression?
BP falls later than CO, so additional perfusion parameters must be monitored.
▶Why does auto-infusion fail as shock progresses?
Reduced vessel resistance, increased capillary hydrostatic pressure, and decreased colloid osmotic pressure prevent interstitial fluid from entering the vasculature.
▶What is the consequence of ADH and catecholamine depletion in progressive shock?
Loss of vasoconstrictor and water-retaining support, so BP and volume can no longer be maintained.
▶Why does a falling renal medullary osmotic gradient worsen progressive shock?
It impairs urine concentration, so less fluid is retained and volume depletion accelerates.
▶What is the ultimate endpoint of irreversible circulatory shock?
Multiple organ failure / multiple organ dysfunction syndrome (MOF/MODS) and death.
▶Why is the progression of shock considered self-amplifying?
Each vicious cycle (coronary, cerebral, venous pooling, vessel-wall hypoxia) further reduces perfusion, reinforcing the others until decline becomes self-sustaining.
▶How does lysosome destabilization contribute to cell death in shock?
Cell swelling from ATPase failure destabilizes lysosomes, releasing enzymes that cause cell necrosis.
▶What role do tissue-derived vasodilator metabolites play in progressive shock?
They cause vasodilation and venous pooling, reducing venous return and reinforcing the fall in CO.
▶How does increased capillary permeability accelerate progressive shock?
It causes edema and loss of intravascular fluid/electrolytes, lowering blood volume and venous return.
▶What two broad mechanisms together produce irreversibility in shock?
Hemodynamic positive-feedback vicious cycles and metabolic derangement (acidosis + mitochondrial/ATP failure causing necrosis).