Lecture Notes on Shock and Heart Failure

Refractory Vasodilatory Shock

  • Pathophysiologic Mechanisms:
    • Light blue: Initial physiologic result.
    • Dark blue: Shared pathophysiologic mechanisms.
    • Red: End result.
    • Hypoxia leads to:
      • Acidosis
      • Hyperlactatemia (lactic acidosis)
      • ATP sensitive potassium channel activation
      • Membrane hyperpolarization
      • Cellular relaxation
      • Vascular relaxation
      • Impaired responsiveness to catecholamines
      • Refractory vasodilatory shock
    • Dysregulated nitroxyl metabolism:
      • Altered microcirculatory flow
      • Decreased bactericidal activity
      • Coagulation modulation
      • Dysregulated mitochondrial respiration
      • Hyperglycemia
      • Hypocalcemia
      • Refractory vasodilatory shock
    • Reactive Oxygen Species (ROS) overproduction:
      • Endothelial dysfunction
      • Mitochondrial dysfunction
      • Vascular smooth muscle relaxation
      • Control production of nitric oxide and prostaglandin I2
      • Refractory vasodilatory shock
  • Clinical Progression:
    • Hypovolemic or septic shock can lead to death soon after onset.
    • Some patients recover through compensatory mechanisms.
    • Refractory shock (formerly known as irreversible shock) is now treatable due to better understanding of pathophysiology.
  • Factors Contributing to Refractory State:
    • Precapillary sphincters constrict then relax.
    • Postcapillary venules remain constricted.
    • Blood flows into capillaries but does not circulate.
  • Positive Feedback Mechanisms:
    • Cerebral ischemia depresses vasomotor and cardiac discharge, causing blood pressure to fall.
    • Myocardial blood flow is reduced, leading to myocardial failure.
  • Complications:
    • Pulmonary damage and acute respiratory distress syndrome (ARDS) due to capillary endothelial cell damage and alveolar epithelial cell damage with cytokine release.

Syncope (Fainting)

  • Definition: Temporary, self-limited loss of consciousness, usually leading to a fall.
    • 30% of adults experience at least one episode.
    • Prognosis is favorable except in cardiac disease.
  • Evaluation:
    • History is most important to identify the cause.
  • Types:
    • Reflex neurally mediated syncope
    • Orthostatic postural hypertension
    • Cardiogenic syncope

Reflex Neurally Mediated Syncope

  • Due to excessive vagal tone or impaired reflex control of peripheral circulation.
    • Most frequent type: Vasovagal syncope (common faint)
      • Initiated by stressful, painful, or claustrophobic experiences
    • Enhanced vagal tone:
      • Carotid sinus hypersensitivity
      • Post-micturition syncope
        • syncope during or after urination
        • Parasympathetic activation → ↓ heart rate, ↓ blood pressure

Orthostatic Postural Hypertension

  • Common cause of vasodepressor syncope, especially in older population, diabetic patients, or autonomic neuropathy.
    • Chronic idiopathic orthostatic hypotension primarily in older men.
    • Impaired vasoconstrictive response to upright posture.
    • Inability to compensate for decreased venous return.

Cardiogenic Syncope

  • Mechanical or arrhythmic basis.
    • Injury secondary to falling is common.
    • Often no prodrome.
  • Mechanical problems:
    • Aortic stenosis
    • Pulmonary stenosis
    • Hypertrophic cardiomyopathy
    • Congenital lesions with pulmonary hypertension or right-to-left shunting
    • LA myxoma (benign tumor in left atrium)
  • Arrhythmias
    • Sick sinus syndrome
    • Conduction disorders
    • AV block
    • Tachyarrhythmias (ventricular tachycardia, supraventricular tachycardia)
Orthostatic Hypotension Details
  • Defined as reduction in systolic blood pressure of at least 2020 mmHg or diastolic blood pressure of at least 1010 mmHg within three minutes of standing.
    • Gradual fall in blood pressure without compensatory heart rate increase.
Categories of Syncope (Harrison's Table)
  • Neural Mediated
    • Vasovagal syncope
  • Orthostatic Hypotension
    • Primary autonomic failure
    • Secondary autonomic failure (chronic disorders)
  • Cardiac Syncope
    • Arrhythmias
    • Cardiac Structural Diseases
      • Myocardial ischemia
      • Atrial myxoma
      • Pericardial effusion and tamponade

Left Heart Failure

  • Inadequate pump function of the heart leading to congestion from fluid in lungs and peripheral tissues.
  • Common end result of many cardiac disease processes.
  • Clinical presentation varies.

Causes of Left Ventricular Failure

  • Volume Overload: Valvular problems (regurgitation).
  • High Output States: Anemia, hyperthyroidism.
  • Pressure Overload: Hypertension.
  • Outflow Obstruction: Aortic stenosis, septal hypertrophy.
  • Loss of Muscle: Myocardial infarction, connective tissue diseases (lupus).
  • Loss of Contractility: Alcohol, cobalt, radiation, doxorubicin (chemotherapy).
  • Infections: Viral myocarditis.
  • Genetic Mutations: Sarcomeric proteins.
  • Restricted Filling: Mitral stenosis, pericardial tamponade, restrictive cardiomyopathy (amyloidosis).

Pathophysiology of Left Ventricular Failure

  • Complex dysfunction of the heart as a common endpoint for many cardiovascular diseases.
  • Inappropriate workloads (volume/pressure overload), restricted filling, myocyte loss, or decreased myocyte contractility.
  • In developed countries, the most common cause of myocyte loss is cell death due to obstructed arteries (atherosclerosis, myocardial infarction).

Pathophysiologic Changes Associated with Heart Failure

  • Hemodynamic Changes
  • Hormonal and Nervous System Changes
  • Cellular Changes
Hemodynamic Changes
  • Decreased output, systolic dysfunction, and filling.
  • Sympathetic system activation.
  • Renin-angiotensin-aldosterone system (RAAS) activation.
  • Vasopressin release.
  • Cytokine release.
Cellular Changes
  • Inefficient intracellular calcium handling.
  • Adrenergic desensitization.
  • Myocyte hypertrophy.
  • Re-expression of fetal phenotype proteins.
  • Cell death (apoptosis).
  • Fibrosis
Systolic Dysfunction
  • Shift of isovolumic pressure-volume curve to the right.
  • Ventricle compensates by shifting the diastolic pressure-volume relationship rightward.
  • Increasing contractile state via catecholamines.
  • Increasing filling or preload.
Compensatory Mechanisms
  • Increased return of blood to the heart (preload).
  • Increase in catecholamine release to increase cardiac output.
  • Cardiac muscle hypertrophy and ventricular volume increase.
  • Limited ability to maintain cardiac output leading to heart failure.
Diastolic Dysfunction
  • Diastolic pressure-volume relationship is shifted upward and to the left.
  • Elevated left ventricular end-diastolic pressure.
  • Reduced stroke volume.
  • Can be present with decreased relaxation, decreased elastic recoil, or increased ventricular stiffness.
  • Hypertension often leads to diastolic dysfunction.
  • Ischemia can also cause diastolic dysfunction.
  • Severe ischemia (myocardial infarction) leads to irreversible damage.

Neurohormonal Changes in Left Heart Failure

  • Increased secretion of neurohormones and cytokines due to heart injury.
  • Increased adrenergic activity and RAAS.
  • Elevated plasma norepinephrine levels cause increased cardiac contractility and heart rate.
    • Increased preload, vasoconstriction, arterial vasoconstriction.
Renal Involvement
  • Reduced renal blood pressure stimulates renin release (RAAS).
  • RAAS leads to vasoconstriction and reduced cardiac output/glomerular filtration rate.
  • Increased vasopressin release (vasoconstrictive and promotes reabsorption of water).
  • Cytokine release (interleukin-1 accelerates myocyte hypertrophy, endothelin leads to potent vasoconstriction).

Cellular Changes at Myocyte Level

  • Changes in calcium handling, adrenergic receptors, contractile apparatus, and myocyte structures.
  • Decreased levels of messenger ribonucleic acid.
  • Abnormal calcium concentrations inside the cells.
Adrenergic Receptors
  • Alpha-1: Important for inducing myocardial hypertrophy.
  • Beta adrenergic: Significant desensitization as a result of chronic sympathetic activity.
  • Cardiac myocytes cannot proliferate once matured to their adult form.
  • Myocyte hypertrophy with increased sarcomere numbers.
  • Re-expression of fetal and neonatal forms of myosin troponin.

Right Ventricular Failure

Causes
  • Left ventricular failure (most common).
  • Precapillary obstruction (congenital abnormality, shunts, idiopathic pulmonary hypertension).
  • Primary right ventricular failure (right ventricular infarction).
  • Cor pulmonale (hypoxia-induced vasoconstriction, pulmonary embolisms, COPD).
Pathophysiology
  • Similar to left ventricular failure.
  • Systolic and diastolic abnormalities can be present.
  • Inappropriate loads or impaired myocyte contractility.
  • Patients with isolated right ventricular failure often have pulmonary hypertension or cor pulmonale.
  • The interventricular septum bows toward the thinner-walled right ventricle.