<p> SHOCK and HEART FAILURE 08/12/05</p><p>1. Shock (cardiovasc collapse): the final result for many potentially lethal clinical events including hemorrhage, extensive trauma or burns, large MI, massive pulmonary embolism, and microbial species - Shock gives rise to systemic hypoperfusion caused by reduction either in cardiac output or in the effective circulating blood volume 2. End results of shock: hypotension, followed by impaired tissue perfusion and cellular hypoxia (initially cellular injury is reversible and after a prolonged period causes irreversible tissue injury and possibly death of patient) 3. 3 major categories of shock: Cardiogenic: from myocardial pump failure. Caused by intrinsic myocardial damage (MI), vent arrhythmia, extrinsic compression (tamponade), or outflow obstruction (pulm embolism) Hypovolemic: from blood loss or plasma volume loss. From hemorrhage, fluid loss from burns, or trauma Septic: caused by systemic microbial infection. Usually from gram-negative infections (endotoxic shock), but can occur from gram-positive and fungal infections 4. Neurogenic influences produce shock: anesthetic accident or spinal cord injury = loss of vascular tone and peripheral pooling of blood Anaphylactic influences produce shock: initiated by a generalized IgE-mediated hypersensitivity response = systemic vasodilation and increased vasc permeability 5. Septic Shock: results from spread and expansion of an initially localized infection (abscess, peritonitis, pneumonia) into the bloodstream 6. Gram-negative bacilli: cause 70% of the cases of septic shock. They produce endotoxins = endotoxic shock 7. All of the cellular and hemodynamic effects of septic shock can be accounted for by bacterial wall lipopolysaccharide (LPS) alone. LPS – are endotoxins released when the cell walls of the bacterium are degraded. It consists of a toxic fatty acid core and a complex polysaccharide coat unique to each bacterial species. Causes mononuclear cell activation and production of cytokines = initiation of innate immune system. 8. Fever and increased acute phase reactants repress the effects of TNF and IL-1 9. The four major attributes of high levels of LPS are: 1. Systemic vasodilation 2. Diminished myocardial contractility 3. Endothelial injury causing activation of systemic leukocyte adhesion and pulmonary alveolar capillary damage 4. Activation of the coagulation system = DIC 10. In multiple organ system failure, the organs in which cellular changes are most evident are: liver, kidneys, CNS 11. Toxic Shock Syndrome: caused by staphylococci which cause Superantigens. Superantigens are polyclonal T-lymphocyte activators than induce systemic inflammatory cytokine cascades. Can cause diffuse rash to vasodilation, hypotension, and death 12. 3 Stages of Shock: 1. Non-progressive: reflex compensatory mechanisms are activated and perfusion of vital organs is maintained 2. Progressive: characterized by tissue perfusion and onset of worsening circulatory and metabolic imbalances, including acidosis 3. Irreversible: when body has incurred cell and tissue injury so severe that even if the hemodynamic defects are corrected, survival is not possible 13. Differences in skin changes between: Hypovolemic/Cardiogenic shock: cool and pale skin due to vasoconstriction Septic Shock: warm and flushed skin due to initial cutaneous vasodilation 14. Mortality rate of gram-negative septic shock: 25-50% = 1st among the cause of mortality in ICU; over 200,000 deaths annually in US</p><p>15. 2 types of cardiac dysfunction that can produce heart failure: dysfunction in myocardial contraction (systolic) or in ventricular filling (diastolic) 16. Approximate mortality per year for patients with congestive heart failure (CHF): over 300,000 (affects more than 500,000, and 1 million hospitalizations) Annual cost in US: $18 billion/year 17. The most important mechanisms for cardiovasc system response to an increased burden or decreased cardiac contractility: 1. Frank-Starling Mechanism: the increased preload of dilation helps to sustain cardiac performance by enhancing contractility 2. Myocardial Structural Changes: including augmented muscle mass (hypertrophy) with or without cardiac chamber dilation- mass of contractile tissue is augmented 3. Activation of neurohumoral systems: 1. release of the NE by adrenergic cardiac nerves (increases HR and augments myocardial contractility against vascular resistance), 2. activation of the renin-angio-aldosterone system, and 3. release of ANP 18. 2 most frequent specific causes of systolic dysfunction: 1. Systolic dysfunction: ischemia, pressure of volume overload, dilated Cardiomyopathy 2. Diastolic dysfunction: inability of the heart chamber to relax, expand and fill sufficiently during diastole 19. Difference b/w forward and backward failure (characterize CHF): Forward failure: diminished cardiac output Backward failure: damming of blood back in the venous system 20. Relationship of cardiac hypertrophy and the onset of heart failure: - the molecular and cellular changes in hypertrophied hearts that initially mediates enhanced function may contribute to the development of heart failure o proteins related to contractile elements, excitation-contraction coupling, and energy utilization may be significantly altered through production different isoforms that either may be less functional than normal or may be reduced or increased amount - pattern of hypertrophy reflects the nature of the stimulus - pressure-overloaded ventricles (HTN or aortic stenosis) develop concentric hypertrophy of the L ventricle – this increased diameter of the L ventricle may reduce the cavity diameter - In pressure overload, the deposition of sarcomeres is parallel to the long axes of cells (cross-section is larger, length stays the same) - In volume overload, there is deposition of new sarcomeres and cell length = dilation of ventricle diameter 21. Cardiac hypertrophy represents a tenuous balance b/w which characteristics and alterations: - a tenuous balance b/w adaptive characteristics (new sarcomeres) and potentially deleterious structural and biochemical/molecular alterations (ex/ decreased capillary-to-myocyte ratio, increased fibrous tissue, and synthesis of abnormal proteins) - therefore sustained cardiac hypertrophy often evolves to cardiac failure due to decreased stroke volume and cardiac output</p>