Shock

1. Etiology and classification

• Obstructive shock. Some classifications make this a separate group: tamponade, tension pneumothorax, massive pulmonary embolism. Robbins places these under cardiogenic shock.
• Distributive shock. This group covers septic, neurogenic and anaphylactic shock. The shared problem is vasodilation and maldistribution of flow.
• Related terms.
  • Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection.
  • Septic shock is the subset of sepsis with profound circulatory, cellular and metabolic abnormalities and higher mortality.
  • SIRS is a sepsis-like state triggered by non-infectious insults such as burns, trauma and pancreatitis.

2. Pathogenesis: stages and decompensation

• Reflex compensation keeps perfusion of vital organs.
• Mechanisms are baroreceptor reflexes, catecholamines, ADH, activation of the renin-angiotensin-aldosterone axis, and generalized sympathetic stimulation.
• Net effects are tachycardia, peripheral vasoconstriction and renal fluid conservation.
• Cutaneous vasoconstriction gives cool, pale skin. Early septic shock may instead give warm, flushed skin from vasodilation.
• Coronary and cerebral vessels respond less to sympathetic signals, so blood is shunted to the heart and brain.

• Compensation fails and hypoperfusion becomes widespread.
• Persistent oxygen deficit shifts cells from aerobic respiration to anaerobic glycolysis. Lactic acid accumulates and causes metabolic lactic acidosis.
• Low tissue pH blunts the vasomotor response. Arterioles dilate and blood pools in the microcirculation.
• Pooling lowers venous return and cardiac output. It also exposes endothelium to anoxic injury, which can lead to DIC.
• Vital organs begin to fail.

• Cell injury is severe enough that survival is not possible even if the hemodynamics are corrected.
• Lysosomal enzymes leak and worsen the shock state.
• Myocardial contractility falls further, partly from increased nitric oxide synthesis.
• Ischemic bowel lets intestinal flora enter the circulation, so bacteremic shock may be superimposed.
• Progression to renal failure, with multiorgan failure and death, is common. The textbook text for this last point was partly truncated in my retrieval, so I filled it in from general knowledge.

Pathogenesis by type

• Volume loss lowers preload and cardiac output, and the stages above follow.
• Compensation can maintain blood pressure after about 10 to 15% volume loss. Beyond that, decompensation sets in.

• Pump failure lowers cardiac output despite adequate volume.
• Venous pressures are raised, with congestion.
• Compensatory vasoconstriction raises afterload, which increases myocardial oxygen demand.
• This creates a vicious circle of ischemia and worsening pump failure.

1. Inflammatory and counter-inflammatory responses.
   • PAMPs and DAMPs engage TLRs, G-protein-coupled receptors and C-type lectin receptors. NF-kB is activated.
   • TNF, IL-1, IL-12, IL-18, IFN-γ and HMGB1 are released.
   • Complement is activated, producing C3a and C5a.
   • A counter-regulatory immunosuppression follows, with IL-10, soluble TNF receptor, lymphocyte apoptosis and anergy. Patients may oscillate between hyperinflammatory and immunosuppressed states.
2. Endothelial activation and injury.
   • Tight junctions loosen, causing vascular leak and protein-rich edema.
   • NO, C3a, C5a and PAF cause vasodilation and hypotension.
   • Microvascular flow is heterogeneous and autoregulation is lost, so oxygen delivery does not match need.
3. Procoagulant state.
   • Tissue factor rises. Thrombomodulin, protein C and TFPI fall. PAI-1 rises, which suppresses fibrinolysis.
   • Neutrophil extracellular traps may also promote coagulation.
   • The result is fibrin thrombi in small vessels and DIC in up to half of septic patients. Consumption of factors and platelets then causes bleeding.
4. Metabolic abnormalities.
   • Insulin resistance with hyperglycemia, raised triglycerides and lactic acidosis.
   • Adrenal insufficiency may follow an initial glucocorticoid surge. It can be functional or from adrenal hemorrhagic necrosis (Waterhouse-Friderichsen syndrome).
5. Organ dysfunction.
   • Hypotension, edema, microvascular dysfunction and thrombosis reduce oxygen delivery.
   • Mitochondrial damage impairs oxygen use.
   • Cytokines depress myocardial contractility.
   • Increased permeability and endothelial injury can lead to ARDS.
   • Superantigens (e.g. toxic shock syndrome) cause polyclonal T-cell activation and a similar picture.

• Both cause acute vasodilation, hypotension and tissue hypoperfusion.
• In neurogenic shock, sympathetic tone is lost.
• In anaphylaxis, mast cell mediators (histamine, leukotrienes) act.

3. Morphological features

• Kidney. Acute tubular necrosis (acute kidney injury) is the key lesion and leads to oliguria. Fibrin thrombi are most readily seen in the glomeruli.
• Heart. Hypoxic injury with possible subendocardial hemorrhage and focal or coagulative necrosis of myocytes.
• Brain. Ischemic encephalopathy with neuronal loss, especially in watershed zones.
• Adrenals. Lipid depletion of the cortical cells, a stress reaction from use of stored lipids for steroid synthesis. In DIC with sepsis, hemorrhagic necrosis can occur (Waterhouse-Friderichsen syndrome).
• Lungs.
  • They resist hypoxic injury in hemorrhagic shock.
  • Sepsis or trauma can cause diffuse alveolar damage, called "shock lung": edema, hyaline membranes, then type II pneumocyte hyperplasia.
• Gastrointestinal tract. Mucosal hemorrhagic necrosis ("hemorrhagic enteropathy") and stress ulcers. Barrier loss allows bacterial translocation.
• Liver. Centrilobular hemorrhagic necrosis and fatty change.
• Microvasculature. Fibrin thrombi from DIC may be present in any tissue.
• Recovery. If the patient survives, tissues recover completely except for neuronal and cardiomyocyte loss.

• Hypovolemic and cardiogenic shock give hypotension, a weak rapid pulse, tachypnea, and cool, clammy, cyanotic skin.
• Septic shock may give warm, flushed skin.
• More than 90% of young, healthy patients with hypovolemic shock survive with treatment. Septic and cardiogenic shock have much poorer outcomes. Sepsis mortality is about 40%.