What is the mechanism behind shock?

Mechanisms of Shock

The central pathophysiologic mechanism of shock is diminished cardiac output leading to systemic hypoperfusion, which triggers maladaptive cycles of ischemia, inflammation, vasoconstriction, and volume overload, often culminating in multiorgan system failure and death. 1

Definition and Classification

Shock is defined as acute circulatory failure resulting in decreased organ perfusion with inadequate delivery of oxygenated blood to tissues, leading to end-organ dysfunction 2. Shock can be classified into four main categories based on underlying mechanisms:

1. Hypovolemic Shock

• Results from decreased intravascular volume due to hemorrhage, severe dehydration, or excessive fluid losses 1
• Characterized by decreased preload, reduced cardiac output, and compensatory tachycardia 2

2. Cardiogenic Shock

• Caused by primary cardiac dysfunction leading to impaired cardiac output 1
• Often associated with myocardial infarction involving >40% of left ventricular myocardium 1
• Can also result from mechanical complications such as free wall rupture, ventricular septal defect, or papillary muscle rupture 1
• May develop in patients with longstanding ventricular dysfunction (acute decompensated heart failure with cardiogenic shock) 1

3. Distributive Shock

• Characterized by pathological vasodilation and/or vasoplegia 3
• Includes septic shock, anaphylactic shock, and neurogenic shock 2
• Features vascular hyporeactivity with reduced vascular smooth muscle contraction in response to α1 adrenergic agonists 3

4. Obstructive Shock

• Results from mechanical obstruction to blood flow 2
• Causes include pulmonary embolism, tension pneumothorax, cardiac tamponade, and aortic dissection 2

Pathophysiological Cascade

Initial Insult and Decreased Cardiac Output

• The primary insult (cardiogenic, hypovolemic, distributive, or obstructive) leads to decreased cardiac output 1
• Impaired cardiac output and progressive diastolic dysfunction raise ventricular end-diastolic pressures 1
• Elevated ventricular pressures reduce coronary perfusion pressure, further impairing myocardial contractility and stroke volume 1

Tissue Hypoperfusion and Inflammatory Response

• Inadequate tissue perfusion leads to cellular hypoxia and anaerobic metabolism 4
• Tissue ischemia and necrosis trigger release of inflammatory mediators 1
• These inflammatory mediators impair tissue metabolism and induce nitric oxide production 1
• In distributive shock, nitric oxide causes systemic vasodilation, exacerbating hypotension 1, 3

Vascular Dysfunction Mechanisms

• In vasogenic shock, several mechanisms contribute to vascular dysfunction:
  • Induction of nitric oxide synthases leading to excessive vasodilation 3
  • Activation of ATP-sensitive potassium channels in vascular smooth muscle 3
  • Vasopressin deficiency, particularly in septic shock 1, 5
  • Catecholamine receptor downregulation and desensitization 1

Organ-Specific Effects and Maladaptive Responses

• Pulmonary effects: Hypoxia and inflammation induce pulmonary vasoconstriction, increasing biventricular afterload and myocardial oxygen demand 1
• Renal effects: Impaired glomerular perfusion increases tubular sodium reabsorption and activates the renin-angiotensin-aldosterone system, resulting in volume overload 1
• Splanchnic effects: Sympathetically mediated splanchnic vasoconstriction redistributes blood volume back to circulation, further worsening ventricular filling pressures 1

Progression to Multi-Organ Failure

• Augmented ventricular filling pressures worsen myocardial efficiency and ischemia 1
• This creates a vicious cycle of worsening cardiac function and tissue perfusion 6
• If uninterrupted, this maladaptive cycle progresses to multi-organ system failure and death 1, 4

Neurohormonal and Receptor-Mediated Responses

Catecholamine Response

• Shock triggers release of endogenous catecholamines (epinephrine, norepinephrine) 1
• These act on α and β receptors in vascular smooth muscle and cardiac tissue 1
• α-receptor stimulation causes vasoconstriction while β-stimulation increases inotropy and heart rate 1
• Prolonged shock can lead to catecholamine depletion and receptor desensitization 1

Vasopressin System

• Vasopressin is released from the posterior pituitary in response to hypotension 1
• It acts on V1a receptors to cause vasoconstriction through a catecholamine-independent mechanism 1
• In septic shock, vasopressin deficiency may develop due to depletion of stores and inadequate synthesis 1

Metabolic Derangements

• Shock leads to anaerobic metabolism and lactic acidosis 4
• Acidosis further impairs myocardial function and vascular responsiveness to catecholamines 7
• Glycogenolysis in the liver, free fatty acid release from adipose tissue, and altered insulin release contribute to metabolic dysfunction 1

Special Considerations in Specific Shock Types

Cardiogenic Shock

• Involves a spiral of ischemia causing myocardial dysfunction, which in turn worsens ischemia 6
• Myocardial stunning and hibernation can enhance dysfunction 6
• Often requires inotropic support with agents like dobutamine 1

Septic Shock

• Initially presents with hyperdynamic state (high cardiac output, low systemic vascular resistance) 1
• Later progresses to myocardial depression and multi-organ dysfunction 1
• Characterized by systemic inflammation and vasopressor-resistant hypotension 1

Vasogenic Shock

• Can be the common final pathway for long-lasting, severe shock of any cause 3
• Features vascular hyporeactivity to vasopressors due to multiple mechanisms 3
• May require combination vasopressor therapy targeting different receptor systems 1

Understanding these complex pathophysiological mechanisms is crucial for appropriate management of shock, which should focus on addressing the underlying cause while supporting organ perfusion to prevent irreversible damage and death 4.