Shock: Detailed Overview

• Harrison's Principles of Internal Medicine 22E, p. 2353
• Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 134

Pathophysiology (Cellular Level)

• Glucose is metabolized to lactate instead of entering the TCA cycle
• ATP production drops dramatically (2 ATP/glucose vs. 36-38 in aerobic)
• ATP-dependent Na+/K+ ATPase fails → cellular swelling, ionic dysregulation
• Intracellular calcium influx activates phospholipases and proteases → cell death
• Intracellular contents leak into extracellular space, triggering inflammatory cascades
• Lactic acidosis develops, blunting vasomotor responses

DO₂ = CO × CaO₂ (Cardiac Output × Arterial Oxygen Content)
SV ∝ (Preload × Contractility) / SVR
CaO₂ = (Hb × 1.34 × SaO₂) + (PaO₂ × 0.003)

• Harrison's, p. 2353-2354

Classification of Shock

• Harrison's, p. 2354 (Table 314-2)

1. Distributive Shock

1a. Septic Shock

• Definition: Sepsis (life-threatening organ dysfunction from dysregulated host response to infection) + persistent hypotension requiring vasopressors + elevated lactate despite adequate volume resuscitation
• Organisms: Gram-positive bacteria (most common), gram-negative bacteria, fungi; can follow SARS-CoV-2 and other viral infections
• Pathogenesis:
  • Microbial PAMPs (e.g., endotoxin, enterotoxin B) engage TLRs on innate immune cells
  • Activation of NF-κB → massive cytokine release: TNF, IL-1, IL-6, IL-12, IL-18, IFN-γ, HMGB1
  • Endothelial activation: loosened tight junctions → vascular leak and widespread edema
  • Upregulation of nitric oxide (NO) and vasodilatory mediators → profound vasodilation
  • Procoagulant state: increased tissue factor, decreased thrombomodulin and protein C → DIC in up to 50% of patients
  • Metabolic derangements: insulin resistance, hyperglycemia, lactic acidosis
  • Counter-inflammatory immunosuppression may follow the initial cytokine storm (oscillation between hyper- and hypoinflammatory states)
• Hemodynamic profile: Initially warm, flushed skin (vasodilation), high CO, low SVR; later may become cold and clammy as cardiac function deteriorates
• Mortality: ~40% despite modern critical care
• Robbins, Cotran & Kumar, p. 135-137

1b. Anaphylactic Shock

• Trigger: IgE-mediated hypersensitivity reaction to allergens (food, drugs, insect stings)
• Mechanism: Massive histamine release from mast cells and basophils → profound venous and arterial vasodilation; up to 35% of circulating blood volume can extravasate within 10 minutes
• Features: Urticaria, angioedema, bronchospasm, hypotension; can be rapidly fatal
• Treatment: Epinephrine is the cornerstone

1c. Neurogenic Shock

• Trigger: Severe brain or spinal cord injury
• Mechanism: Disruption of autonomic pathways regulating vascular tone → loss of sympathetic vasoconstriction → venous pooling → reduced venous return and decreased CO
• Characteristic feature: Hypotension with bradycardia (loss of sympathetic tone) - distinguishes it from other shock types that typically cause tachycardia; also presents with hypothermia and wide pulse pressure
• Harrison's, p. 2354; Harriet Lane Handbook

1d. Endocrine (Adrenal) Shock

• Cause: Adrenal insufficiency - from chronic steroid use, immune checkpoint inhibitors, metastatic malignancy, adrenal hemorrhage, TB, HIV, autoimmune adrenalitis, amyloidosis
• Mechanism: Inability to increase cortisol in stress states → vasodilation; aldosterone deficiency → hypovolemia
• Often recognized during superimposed stress (infection, surgery)

1e. Other Distributive Causes

• Severe pancreatitis, extensive burns, liver failure - mediated by inflammatory mediator release
• Harrison's, p. 2354

2. Cardiogenic Shock

Causes:

• Intrinsic myocardial damage: Acute MI (most common), myocarditis, cardiomyopathy
• Mechanical complications: Ventricular rupture, acute mitral regurgitation, VSD
• Arrhythmias: Sustained VT/VF, complete heart block
• Extrinsic compression: Cardiac tamponade
• RV failure: Massive pulmonary embolism, RV infarction

Hemodynamic Profile:

• Left ventricular involvement: ↑ PCWP, ↑ CVP, ↓ CO, ↑ SVR
• Right ventricular involvement: ↑ CVP, ↓ PCWP, ↓ CO, ↑ SVR

Clinical Features:

• Cold, clammy skin, weak rapid pulse, hypotension
• Pulmonary edema (in LV failure) - differentiates from hypovolemic shock
• Jugular venous distension (JVD), S3 gallop
• Oliguria, altered mental status

Management:

• Treat the underlying cause (reperfusion in MI, pericardiocentesis in tamponade)
• Inotropes (dobutamine), vasopressors (norepinephrine)
• Mechanical circulatory support (IABP, Impella, ECMO) in refractory cases
• Robbins, Cotran & Kumar, p. 134; Harrison's p. 2354

3. Hypovolemic Shock

Causes:

1. Hemorrhagic (most common in trauma):
   • External bleeding (lacerations, penetrating trauma)
   • Internal bleeding (GI hemorrhage, ruptured aortic aneurysm, ectopic pregnancy, splenic rupture, pelvic fractures)
2. Non-hemorrhagic:
   • Fluid loss: vomiting, diarrhea, fistula drainage, excessive diuresis
   • Burns (massive plasma protein loss)
   • Third-spacing (pancreatitis, bowel obstruction, peritonitis)

ATLS Classification of Hemorrhagic Shock:

• Sabiston Textbook of Surgery, p. 567 (Table 33.1)

Clinical Features:

• Cold, clammy, pale skin (sympathetic vasoconstriction)
• Tachycardia, hypotension, narrow pulse pressure
• Oliguria (renal vasoconstriction)
• Flat neck veins (low venous pressure)
• No pulmonary edema (distinguishes from cardiogenic)

4. Obstructive Shock

Causes:

• Cardiac tamponade: Pericardial fluid compresses the heart; Beck's triad (hypotension, JVD, muffled heart sounds)
• Tension pneumothorax: Mediastinal shift compresses the great veins, reducing venous return
• Constrictive pericarditis: Chronic pericardial fibrosis restricts diastolic filling

• Massive pulmonary embolism: Right heart obstruction
• Venous air embolism / fat embolism: Right heart obstruction
• Aortic dissection: Left ventricular outflow obstruction
• Severe aortic stenosis

Hemodynamic Profile:

• ↑ CVP (elevated right-sided pressures)
• PCWP variable (↓ in PTX/tamponade, ↑ in LV outflow obstruction)
• ↓ CO, ↑ SVR

Clinical Features:

• JVD with hypotension (key clue)
• Tracheal deviation and absent breath sounds (tension PTX)
• Pulsus paradoxus (tamponade)
• Clinical urgency: must be recognized and treated immediately (needle decompression, pericardiocentesis, thrombolytics)
• Harrison's, p. 2354; Tintinalli's Emergency Medicine; Washington Manual

5. Mixed Shock

• Sepsis may cause distributive shock AND secondary cardiogenic shock (sepsis-induced cardiomyopathy)
• Trauma may cause hypovolemic shock AND obstructive shock (tension pneumothorax)
• The dominant type should guide initial therapy while addressing all components
• Harrison's, p. 2354

Stages of Shock (Any Type)

Stage 1: Nonprogressive (Compensated)

• Neurohumoral compensatory mechanisms activated: baroreceptor reflexes, catecholamine release, ADH, RAAS activation, generalized sympathetic stimulation
• Net result: tachycardia, peripheral vasoconstriction, renal fluid conservation
• Blood is shunted from skin to vital organs (heart and brain)
• Skin is cool, pale (except septic shock - may be warm and flushed)
• Vital organ perfusion maintained; recovery possible without major intervention

Stage 2: Progressive

• If underlying cause not corrected, tissue hypoxia worsens
• Anaerobic glycolysis → lactic acid accumulation → metabolic acidosis
• Arterioles dilate; blood pools in microcirculation
• Endothelial cells at risk for anoxic injury → potential DIC
• Vital organs begin to fail

Stage 3: Irreversible

• Widespread cell injury; lysosomal enzyme leakage further worsens the state
• Myocardial contractility deteriorates (increased NO synthesis)
• Ischemic bowel allows intestinal flora to enter circulation → superimposed bacteremic shock
• Renal failure (acute tubular necrosis)
• Despite maximal intervention, death occurs
• Robbins, Cotran & Kumar, p. 137; Guyton & Hall Medical Physiology

Morphological Changes in Shock (Pathology)

• Robbins, Cotran & Kumar, p. 137

Clinical Features Summary

General Management Principles

1. Identify and treat the underlying cause - this is the single most important intervention
2. Airway and oxygenation - secure airway, supplemental O₂, consider intubation
3. Vascular access - large-bore IV or central venous access
4. Fluid resuscitation:
   • Hypovolemic: crystalloids first, then blood products (Class III-IV hemorrhage)
   • Cardiogenic: cautious fluids (risk of worsening pulmonary edema)
   • Septic: 30 mL/kg crystalloid within 3 hours (Surviving Sepsis guidelines)
   • Obstructive: definitive treatment of obstruction (pericardiocentesis, needle decompression)
5. Vasopressors: Norepinephrine is first-line for most shock states requiring vasopressor support; target MAP ≥65 mmHg
6. Inotropes: Dobutamine for cardiogenic shock with low CO
7. Specific therapies:
   • Epinephrine for anaphylaxis
   • Antibiotics + source control for sepsis
   • Reperfusion (PCI/thrombolytics) for MI
   • Needle decompression for tension pneumothorax
   • Pericardiocentesis for cardiac tamponade
8. Monitor: Lactate clearance, urine output, MAP, mental status as endpoints of resuscitation

• Harrison's Principles of Internal Medicine 22E (2025), Chapter 314
• Robbins, Cotran & Kumar Pathologic Basis of Disease, Chapter 4
• Sabiston Textbook of Surgery, Chapter 33
• Guyton & Hall Textbook of Medical Physiology
• Tintinalli's Emergency Medicine; Washington Manual of Medical Therapeutics

• 4 color-coded columns for each shock type (Distributive, Cardiogenic, Hypovolemic, Obstructive) with their mechanisms, causes, hemodynamic profiles, clinical features, and first-line treatments
• Hemodynamic arrows (CO, SVR, CVP, PCWP) for quick differentiation at a glance
• 3 stages of shock progression at the bottom: Nonprogressive → Progressive → Irreversible