Shock

1. Etiology and classification

• Sepsis: life-threatening organ dysfunction caused by a dysregulated host response to infection.
• Septic shock: a subset of sepsis with profound circulatory, cellular, and metabolic abnormalities and a higher mortality, about 40%.
• SIRS: a sepsis-like state from non-infectious insults such as burns, trauma, or pancreatitis.

• Hypovolemic, cardiogenic, and obstructive shock: low cardiac output with high systemic vascular resistance (cold shock).
• Distributive shock: low systemic vascular resistance with initially high or normal cardiac output (warm shock).

2. Pathogenesis

A. Stages of shock and decompensation

• Baroreceptor reflexes, catecholamine and ADH release, and renin-angiotensin-aldosterone activation maintain cardiac output and blood pressure.
• The result is tachycardia, peripheral vasoconstriction, and renal salt and water retention.
• Cutaneous vasoconstriction causes cool, pale skin.
• Coronary and cerebral vessels respond poorly to sympathetic signals, so flow to the heart and brain is preserved (blood is shunted to vital organs).
• Early septic shock may instead show warm, flushed skin because of cutaneous vasodilation.

• Persistent hypoxia switches cells to anaerobic glycolysis, producing lactic acid and metabolic acidosis.
• Acidosis blunts the vasomotor response. Arterioles dilate and blood pools in the microcirculation.
• Pooling lowers cardiac output further and exposes endothelium to anoxic injury, which can lead to DIC.
• Vital organs begin to fail.
• This is the decompensation point. Compensatory vasoconstriction fails, and a vicious circle of falling output, worsening hypoxia, and worsening acidosis sets in.

• Lysosomal enzymes leak from injured cells and worsen the shock.
• Myocardial contractility falls, partly because of increased nitric oxide synthesis.
• Ischemic bowel lets intestinal flora enter the circulation, so bacteremic shock can be superimposed.
• Ischemic renal failure follows, and the patient dies even if the hemodynamic defect is corrected.

B. Mechanisms by type

• Volume loss lowers venous return, stroke volume, and cardiac output.
• The compensatory stage described above follows, then decompensation if volume is not replaced.
• In trauma and burns, ongoing plasma loss into injured tissue and mediator release can keep the shock progressing even after bleeding stops (Mulholland and Greenfield's Surgery, Traumatic Shock).

• The pump fails, or filling or outflow is blocked.
• Cardiac output falls despite adequate or high filling pressures.
• Compensatory vasoconstriction increases afterload and myocardial oxygen demand. This worsens ischemia and forms a vicious circle.

1. Inflammatory and counter-inflammatory responses
   • Microbial products (PAMPs) and DAMPs bind Toll-like receptors, G-protein-coupled receptors, and C-type lectin receptors.
   • This activates NF-kB and releases TNF, IL-1, IL-12, IL-18, IFN-γ, and HMGB1.
   • Reactive oxygen species, prostaglandins, and PAF are also produced.
   • Complement is activated (C3a, C5a, C3b).
   • Factor XII activates coagulation.
   • Counter-regulatory immunosuppression runs in parallel, through IL-10, soluble TNF receptor, IL-1 receptor antagonist, lymphocyte apoptosis, and anergy. Patients can swing between hyperinflammation and immunosuppression.
2. Endothelial activation and injury
   • Tight junctions loosen, causing vascular leak and protein-rich edema.
   • Increased NO, C3a, C5a, and PAF relax vascular smooth muscle and cause hypotension.
   • Microvascular dysfunction (intermittent capillary flow, lost autoregulation) mismatches oxygen delivery and demand.
3. Procoagulant state
   • Tissue factor increases.
   • Tissue factor pathway inhibitor, thrombomodulin, and protein C decrease.
   • PAI-1 rises and suppresses fibrinolysis.
   • Neutrophil extracellular traps (NETs) promote coagulation.
   • The result is fibrin thrombi in small vessels. DIC occurs in up to half of septic patients and can cause bleeding once factors and platelets are consumed.
4. Metabolic abnormalities
   • Insulin resistance (reduced GLUT-4 expression) and hyperglycemia, with raised triglycerides and lactate.
   • Hyperglycemia impairs neutrophil function.
   • An early glucocorticoid surge may be followed by adrenal insufficiency, or by adrenal hemorrhagic necrosis from DIC (Waterhouse-Friderichsen syndrome).
   • Lactic acidosis from impaired oxidative phosphorylation.
5. Organ dysfunction
   • Hypotension, edema, microthrombi, and mitochondrial damage reduce oxygen delivery and use.
   • Cytokines depress myocardial contractility.
   • The end result is multiorgan failure.

• Both cause acute vasodilation with pooling of blood and relative hypovolemia.
• In anaphylaxis, mast-cell mediators (histamine and others) also raise vascular permeability.

3. Morphology

• Organs mainly affected: brain, heart, kidneys, adrenals, and gastrointestinal tract.
• Brain: ischemic encephalopathy, with neuronal loss in vulnerable regions.
• Heart: coagulative necrosis or subendocardial ischemic change, with contraction band necrosis in some areas.
• Kidney: acute tubular necrosis (ischemic type), the cause of oliguria and renal failure. Fibrin thrombi are most easily seen in the glomeruli, especially in DIC.
• Adrenal: lipid depletion of cortical cells, reflecting the stress response and use of stored lipid for steroid synthesis. In meningococcal sepsis with DIC, bilateral hemorrhagic necrosis may occur (Waterhouse-Friderichsen syndrome).
• Lungs:
  • Lungs are usually resistant to hypoxic injury in simple hemorrhagic hypovolemic shock.
  • Sepsis or trauma can cause diffuse alveolar damage ("shock lung"), with hyaline membranes and edema. This is ARDS.
• Gastrointestinal tract: mucosal hemorrhagic necrosis ("hemorrhagic enteropathy"), stress ulcers, and bacterial translocation.
• Liver: centrilobular hemorrhagic necrosis ("shock liver").
• DIC: fibrin microthrombi in many tissues, with petechiae and ecchymoses from consumption coagulopathy.
• Reversibility: apart from neuronal and cardiomyocyte loss, affected tissues can recover completely if the patient survives.

• Hypovolemic and cardiogenic shock: hypotension, weak rapid pulse, tachypnea, and cool, clammy, cyanotic skin.
• Septic shock: the skin may be warm and flushed because of peripheral vasodilation.
• Complications: acute renal failure, ARDS, DIC, and multiorgan failure.
• Prognosis: depends on the cause and duration. Most patients with hypovolemic shock survive with prompt treatment. Mortality in septic shock is about 40%.

Recent evidence check