General Principles of Pathophysiology

General Principles of Pathophysiology Energy Metabolism Perfusion Shock

Topics • Define shock in terms of cellular function • Review the requirements for adequate cellular perfusion (Fick principle) • Review the mechanisms for starling’s law • Preload vs. afterload • Muscle contraction

Topics Continued • Discuss the mechanisms for oxygen transport • oxyhemoglobin dissociation curve • Define the stages of shock • Describe different causes of shock • Define multiple organ dysfunction syndrome

Shock Defined • Inadequate tissue perfusion • Anaerobic metabolism Final Common Pathway!

6 O2 GLUCOSE Aerobic Metabolism 6 CO2 6 H2O METABOLISM 36 ATP HEAT (417 kcal)

Anaerobic Metabolism 2 LACTIC ACID GLUCOSE METABOLISM 2 ATP HEAT (32 kcal)

Inadequate Energy Production Anaerobic Metabolism Lactic Acid Production Metabolic Failure Cell Death! Metabolic Acidosis Anaerobic? So What? Inadequate Cellular Oxygenation

Homeostasis is maintenance of balance • Requires proper functioning systems • Cardiovascular • Respiratory • Renal

Physiology of Perfusion • Dependant on 3 components of circulatory system • Pump • Fluid • Container

Factors Affecting The Pump • Preload • Contractile force • Frank-starling mechanism • Afterload

What Is Blood Pressure? BP = Cardiac Output X Systemic Vascular Resistance CO = Stroke Volume X Heart Rate

What Affects Blood Pressure? • ANS balance • Contractility • Preload • Starling’s law • Afterload

 peripheral vascular resistance… •  afterload… •  blood pressure. Changes in Afterload and Preload  •  Peripheral vasoconstriction…

 peripheral vascular resistance… •  afterload… •  blood pressure. Changes in Afterload and Preload •  Peripheral vasodilation…

 preload… •  contractility (Starling’s Law)… •  blood pressure. •  cardiac output. Changes in Afterload and Preload •  fluid volume…

 preload… •  contractility (Starling’s Law)… •  blood pressure. •  cardiac output. Changes in Afterload and Preload •  fluid volume…

Hemostasis • The stoppage of bleeding. • Three methods • Vascular constriction • Platelet plug formation • Coagulation

Coagulation • Formation of blood clots • Prothrombin activator • Prothrombin  thrombin • Fibrinogen  fibrin • Clot retraction

Disseminated Intravascular Coagulation “A systemic thrombohemorrhagic disorder … with evidence of: • Procoagulant activation • Fibrinolytic activation • Inhibitor consumption • End-organ failure” Bick, R.L. Seminars in Thrombosis and Hemostasis 1996

Pathophysiology of DIC • Uncontrolled acceleration of clotting cascade • Small vessel occlusion • Organ necrosis • Depletion of clotting factors • Activation of fibrinolysis • Ultimately severe systematic hemorrhage

Container • Vasculature is continuous, closed and pressurized system • Microcirculation responds to local tissue needs • Blood flow dependent on PVR

Fick Principle • Effective movement and utilization of O2 dependent on: • Adequate fio2 • Appropriate O2 diffusion into bloodstream • Adequate number of RBCs • Proper tissue perfusion • Efficient hemoglobin ‘loading’

Fick Principle • Perfusion = Arterial O2 Content - Venous O2 Content • Affected by: • Hemoglobin levels • circulation of RBCs • distance between alveoli and capillaries • pH and temperature

Causes of Inadequate Perfusion • Inadequate pump • Inadequate preload • Poor contractility • Excessive afterload • Inadequate heart rate • Inadequate fluid volume • Hypovolemia • Inadequate container • Excessive dilation • Inadequate systematic vascular resistance

Responses to Shock • Normal compensation includes: • Progressive vasoconstriction • Increased blood flow to major organs • Increased cardiac output • Increased respiratory rate and volume • Decreased urine output

O2 use Impaired cellular metabolism Anaerobic metabolism Stimulation of clotting cascade & inflammatory response Impaired glucose usage • ATP synthesis  Intracellular Na+ & water • Cellular edema  Vascular volume • Na+ Pump Function Cellular Response to Shock • Tissue perfusion

Stages of Shock • Compensated • Uncompensated • Irreversible

Compensated Shock • Defense mechanisms are successful in maintaining perfusion • Presentation • Tachycardia • Decreased skin perfusion • Altered mental status

Uncompenstated Shock • Defense mechanisms begin to fail • Presentation • Hypotension • Prolonged Cap refill • Marked increase in heart rate • Rapid, thready pulse • Agitation, restlessness, confusion

Irreversible Shock • Complete failure of compensatory mechanisms • Death even in presence of resuscitation

Types of Shock • Hypovolemic • Cardiogenic • Neurogenic • Anaphylactic • Septic

Hypovolemic Shock • “Fluid failure” • Decreased intravascular volume • Causes? • “Third spacing”

Anaphylactic Shock • “Container failure” • Massive & systemic allergic reaction • Large release of histamine • Increases membrane permeability & vasodilation

Septic Shock • “Container failure” • Systemic infection

Multiple Organ Dysfunction System • Progressive dysfunction of two or more organ systems • Caused by uncontrolled inflammatory response to injury or illness • Typically sepsis

References • New York Presbyterian hospital hypertension center: • Http://pc101186.Med.Cornell.edu/htchome/htbk/Htbkindex.htm • Biographics Gallery: http://www.accessexcellence.com/AB/GG/#Anchor-Building-11481 • RAS (Renin-Angiotensin-Aldosterone System): • http://www.science.mcmaster.ca/Biology/4S03/RAS.HTM • A graduate student’s hypertension page: • http://www.teaching-biomed.man.ac.uk/student_projects/2000/mnpm6ven/default.htm

General Principles of Pathophysiology