Pulmonary Embolism: Comprehensive Notes

Anatomy of the Lungs and Its Circulation

  • Anatomy of the Lungs:
    • Paired, spongy organs in the thoracic cavity.
    • Flank the mediastinum.
    • Enveloped by a double-layered pleural membrane:
      • Visceral pleura: adheres to the lung surface.
      • Parietal pleura: lines the thoracic wall.
    • Right Lung:
      • Three lobes: superior, middle, and inferior.
      • Separated by horizontal and oblique fissures.
    • Left Lung:
      • Two lobes: superior and inferior.
      • Separated by the oblique fissure.
      • Features the cardiac notch to accommodate the heart.
  • Airway Structure:
    • Air enters through the trachea.
    • Trachea bifurcates into the right and left main bronchi.
    • Further divisions:
      • Lobar bronchi
      • Segmental bronchi
      • Bronchioles
      • Terminal bronchioles
      • Respiratory bronchioles (leading to alveolar ducts and alveolar sacs).
    • Alveoli:
      • Primary sites for gas exchange.
      • Lined by type I pneumocytes (facilitating gas diffusion).
      • Type II pneumocytes produce surfactant to reduce surface tension.
  • Pulmonary Circulation:
    • Low-pressure, high-flow system.
    • Deoxygenated blood is pumped from the right ventricle into the pulmonary trunk.
    • Pulmonary trunk divides into the right and left pulmonary arteries (supplying each lung).
    • Arteries branch alongside the bronchial tree, forming a dense capillary network around the alveoli.
    • Oxygenated blood returns via pulmonary veins to the left atrium.
  • Bronchial Circulation:
    • Arises from the systemic circulation (typically from the thoracic aorta).
    • Supplies oxygenated blood to the airways, pleura, and supporting lung structures.
    • Bronchial veins drain into the azygos and hemiazygos systems.
    • Some blood enters the pulmonary veins, contributing to the physiological shunt.

Role of Peripheral and Central Chemoreceptors in the Control of Breathing

  • Central Chemoreceptors:
    • Located in the medulla oblongata.
    • Sensitive to changes in the pH of cerebrospinal fluid (CSF), reflecting arterial CO_2 levels.
    • Hypercapnia (increased arterial CO_2):
      • CO_2 diffuses into the CSF, forming carbonic acid and lowering pH.
      • This acidification stimulates central chemoreceptors to increase the rate and depth of ventilation, enhancing CO_2 elimination.
      • H^+ cant cross BBB but CO2 can. CO2 combines with H2O forming bicarbonate and Hydrogen ions > then the H ions are detected by the central chemoreceptors leading to signals being sent the the respiratory center increasing the rate and depth of ventilation, enhancing CO2 elimination.
      • Responds to Direct > CSF pH indirect > blood CO_2
  • Peripheral Chemoreceptors:
    • Located in the carotid bodies (at the bifurcation of the common carotid arteries) and in the aortic bodies (above and below the aortic arch).
    • Connected to the respiratory sensor via CN 9/10.
    • Respond to:
      • Hypoxemia: A significant decrease in arterial O2 tension (PaO2 < 60 mmHg) increase sensory discharge > CN carries signals to the respiratory center > stimulates these receptors to increase ventilation.
      • Hypercapnia and Acidosis: Elevated CO_2 and decreased pH also stimulate peripheral chemoreceptors, though their response is less pronounced compared to central chemoreceptors.
  • Integration of Chemoreceptor Responses:
    • Afferent signals from peripheral chemoreceptors travel via the glossopharyngeal (cranial nerve IX) and vagus (cranial nerve X) nerves to the respiratory centers in the medulla.
    • Integrate with inputs from central chemoreceptors to modulate respiratory activity appropriately.

Causes of Pulmonary Embolism (PE) and the Mechanisms by Which They Cause It

  • Etiology of PE:
    • Typically results from thrombi originating in the deep veins of the lower extremities (deep vein thrombosis, DVT).
    • Risk factors include:
      • Venous stasis: Prolonged immobility, heart failure.
      • Vascular-Endothelial injury: Trauma, surgery.
      • Hypercoagulable states: Inherited thrombophilias (e.g., Factor V Leiden), malignancy, pregnancy, oral contraceptive use.
      • Causes: Fibroligion increase, Protein c increase Vascular-Endothelial injury > exposure to collagen and tissue factor > platelet aggregation and activation of clotting factors > clot formation
  • Primary Cause:
    • Thromboembolism: The most common cause of PE is a thrombus (blood clot) originating from deep vein thrombosis (DVT), typically in the lower extremities.
    • The clot dislodges, travels through the venous system, passes through the right heart, and lodges in the pulmonary arteries, obstructing blood flow
  • Other Causes:
    • Fat Embolism: Fat droplets entering the circulation, often after long bone fractures, can occlude pulmonary vessels.
    • Air Embolism: Air bubbles introduced into the circulation, possibly during surgical procedures or trauma, can obstruct pulmonary arteries.
    • Amniotic Fluid Embolism: Amniotic fluid entering maternal circulation during labor can cause embolization.
    • Septic Embolism: Infected material from endocarditis or other infections can embolize to the lungs.
    • Tumor Embolism: Fragments of tumors can enter the circulation and lodge in pulmonary vessels.
  • Embolism Causes:
    • Pregnancy: fetus pushes against the veins where its growing > slowing down the blood flow > aggregation of platelets and activation of clotting factors > clot formations
    • Surgery: endothelial cells injury > exposure to collagen and tissue factor > platelet aggregation and activation of clotting factors > clot formation
    • Oral contraceptives: increase clotting factors 7 and 10, decrease levels to anti-coagulation factors > increase the chance of clot formation
    • Prolonged period of inactivity: decrease blood function of skeletal muscle pump > blood flow decreases > increases chances of platelet contact with the endothelial cells > activation of clotting factors > increase clot formation chances
    • Genetic causes: antithrombin-3 deficiency > result of a genetic mutation > increases chances of clot formation
  • Mechanism of PE Formation:
    • A thrombus formed in the deep veins can dislodge, becoming an embolus that travels through the venous system to the right heart and into the pulmonary arteries.
    • The embolus lodges in a pulmonary artery, obstructing blood flow to lung tissue, leading to ventilation-perfusion mismatch, hypoxemia, and increased pulmonary vascular resistance.

Hemodynamic Changes Following PE and Their Physiological Basis

  • Increased Pulmonary Vascular Resistance:
    • Obstruction of pulmonary arteries by emboli increases pulmonary vascular resistance, leading to elevated pulmonary artery pressures.
  • Right Ventricular Strain:
    • The right ventricle faces increased afterload, leading to dilation and impaired contractility.
    • This can result in right ventricular failure and decreased left ventricular preload due to reduced pulmonary blood flow.
    • Increased pressure in the right atrium > increase in central venous pressure
  • Systemic Hypotension:
    • Reduced left ventricular output leads to systemic hypotension, which can progress to shock if not promptly managed.
  • Ventilation-Perfusion Mismatch:
    • Areas of the lung receive ventilation but lack perfusion due to vascular obstruction, leading to inefficient gas exchange and hypoxemia.
  • Neurohumoral Activation:
    • The body responds to decreased oxygenation and perfusion by activating sympathetic pathways, releasing catecholamines that increase heart rate and contractility, attempting to maintain perfusion.
  • JDP:
    • embolism > pulmonary enlargement > RV volume increase > chamber size increases/enlargement > stretch of tricuspid valve > regurgitation > decreases RA blood volume > visible JD/increased JDP

Clinical Features of PE and Their Physiological Basis

  • Dyspnea:
    • Sudden onset of shortness of breath is the most common symptom, resulting from impaired gas exchange due to ventilation-perfusion mismatch.
  • Pleuritic Chest Pain:
    • Sharp, localized chest pain exacerbated by inspiration occurs due to inflammation of the pleura overlying infarcted lung tissue.
  • Tachypnea and Tachycardia:
    • Compensatory responses to hypoxemia and decreased cardiac output.
  • Hemoptysis:
    • Coughing up blood may occur if pulmonary infarction leads to alveolar hemorrhage.
  • Syncope:
    • Transient loss of consciousness can result from sudden hemodynamic compromise due to massive PE.
  • Signs of DVT:
    • Swelling, pain, and redness in the lower extremities may indicate the source of emboli.
  • Small embolism:
    • affects blood vessels only
  • Large embolism:
    • Obstruction of large/major arteries > acute pulmonary hypertension > RV failure

Changes in Arterial Blood Gases After Major PE and Their Physiological Basis

  • Hypoxemia (Low PaO_2):
    • Due to areas of the lung being ventilated but not perfused (dead space), leading to impaired oxygenation.
  • Hypocapnia (Low PaCO_2):
    • Hyperventilation in response to hypoxemia leads to excessive CO_2 elimination.
  • Respiratory Alkalosis:
    • The decreased PaCO2 (partial pressure of CO2 in arterial blood) raises blood pH, resulting in alkalosis.
  • Increased Alveolar-Arterial (A-a) Gradient:
    • Reflects impaired oxygen transfer from alveoli to blood, indicative of V/Q mismatch.

Pathogenesis of Pulmonary Edema After PE to Include Both Exudate and Transudate Edema

  • Transudative Pulmonary Edema:
    • Occurs due to increased hydrostatic pressure in pulmonary capillaries secondary to right ventricular failure, leading to fluid transudation into alveolar spaces.
  • Mechanism:
    • Pulmonary infarction and inflammation increase capillary permeability, allowing protein-rich fluid to leak into alveolar spaces.
  • Characteristics:
    • High protein content, presence of inflammatory cells, and often associated with pleuritic chest pain and hemoptysis.
    • Embolism > obstruction of blood flow > increase pressure behind the embolism > increase hydrostatic pressure > fluid transduction into the alveolar spaces
    • Increase capillaries and small blood vessels pressure (behind the embolism) > blood vessel bursting > blood leaking into the alveolar space > embolus in artery → obstruction of blood flow → pulmonary hypertension → increased hydrostatic pressure behind obstruction → a) plasma leaks out into lung tissue → b) small capillaries burst → blood enters lung tissue (NOT CHEST PAIN)
  • Exudative Pulmonary Edema:
    • Results from increased capillary permeability due to inflammatory mediators released in response to ischemia or infarction, allowing protein-rich fluid to enter the alveoli.
  • Mechanism:
    • Elevated pulmonary capillary hydrostatic pressure due to increased PVR and right heart strain leads to fluid transudation into alveoli.
  • Characteristics:
    • Low protein content, absence of significant inflammation, and often associated with systemic signs of fluid overload.
  • Intravascular:
    • embolism causes injury to the vascular endothelial cells > inflammation within the blood vessel> release of il-1, il-2, tnf1 > increase nitric oxide, decrease endothelin and thromboxane 2 > vasodilation
    • Causes increase vascular permeability > increase inflammatory cells and markers leaving the blood vessel, goes into the lung tissue > edema
    • Intravascular: embolus impact inside artery → endothelial injury in vessel → inflammation → release of cytokines → phosphorylation of endothelial cadherins → increases vascular permeability → leakage of inflammatory cells and markers into lung tissue → oedema
  • Extravascular:
    • embolus impact inside artery → impaired blood flow → ischemia of bronchioles and lung tissue (distal to obstruction) → inflammation → oedema
  • Reason of chest pain:
    • If tissue near pleural membrane affected → inflammation increases the permeability of pleural membrane → entry of cells + mediators into pleural cavity → increased viscosity → pleural rub → activation of nerve endings in parietal pleura → chest pain
    • Obstruction doesn't cause pain it's the inflammation that follows which increases pleural permeability → rub

Clinical Implications

  • Both types of edema can coexist and they both impair gas exchange, lead to hypoxemia, and can lead to respiratory failure if not addressed promptly.
  • Symptoms of patient
    • Pale : decrease in renal perfusion > RAAS activated > angiotensin 2 increases > blood vessel constriction/ vasoconstriction > paleness
    • Sympathetic hyperactivity: Reduce cardiac output > bowel reflex response > sympathetic activation > vasoconstriction > sweating
    • Pleuritic chest pain: increase sympathetic activation > vasoconstriction > pain
    • Reduce cardiac output: decreased BP > hypoperfusion
    • High pulse: hypoxia
    • Low BP: obstruction
    • High RR: activation of chemoreceptors in response to low O2 and high CO2
    • Crackles: result of edema > small airways collapsing > pop open airway xintervention