Pathophysiology of Shock

Definition and Classification

The American College of Cardiology defines shock as acute circulatory failure resulting in decreased organ perfusion with inadequate delivery of oxygenated blood to tissues, leading to end-organ dysfunction, characterized by 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
Hypovolemic shock results from decreased intravascular volume due to hemorrhage, severe dehydration, or excessive fluid losses, characterized by decreased preload, reduced cardiac output, and compensatory tachycardia 2, 3
Cardiogenic shock is caused by primary cardiac dysfunction leading to impaired cardiac output, often associated with myocardial infarction involving >40% of left ventricular myocardium, and can also result from mechanical complications such as free wall rupture, ventricular septal defect, or papillary muscle rupture 1

The primary insult (cardiogenic, hypovolemic, distributive, or obstructive) leads to decreased cardiac output, impaired cardiac output and progressive diastolic dysfunction raise ventricular end-diastolic pressures, and elevated ventricular pressures reduce coronary perfusion pressure, further impairing myocardial contractility and stroke volume 1
Tissue ischemia and necrosis trigger release of inflammatory mediators, which impair tissue metabolism and induce nitric oxide production, and in distributive shock, nitric oxide causes systemic vasodilation, exacerbating hypotension 1
Pulmonary effects of shock include hypoxia and inflammation inducing pulmonary vasoconstriction, increasing biventricular afterload and myocardial oxygen demand, and renal effects include impaired glomerular perfusion increasing tubular sodium reabsorption and activating the renin-angiotensin-aldosterone system, resulting in volume overload 1

Shock triggers release of endogenous catecholamines (epinephrine, norepinephrine), which act on α and β receptors in vascular smooth muscle and cardiac tissue, causing vasoconstriction and increasing inotropy and heart rate 4
Vasopressin is released from the posterior pituitary in response to hypotension, acting on V1a receptors to cause vasoconstriction through a catecholamine-independent mechanism, and in septic shock, vasopressin deficiency may develop due to depletion of stores and inadequate synthesis 4
Metabolic derangements in shock include anaerobic metabolism and lactic acidosis, acidosis further impairing myocardial function and vascular responsiveness to catecholamines, and glycogenolysis in the liver, free fatty acid release from adipose tissue, and altered insulin release contributing to metabolic dysfunction 4

Septic shock initially presents with hyperdynamic state (high cardiac output, low systemic vascular resistance), later progressing to myocardial depression and multi-organ dysfunction, characterized by systemic inflammation and vasopressor-resistant hypotension 6
Vasogenic shock can be the common final pathway for long-lasting, severe shock of any cause, featuring vascular hyporeactivity to vasopressors due to multiple mechanisms, and may require combination vasopressor therapy targeting different receptor systems 5