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!

Aerobic Metabolism

6 O 2 GLUCOSE 6 CO 2 METABOLISM 6 H 2 O 36 ATP HEAT (417 kcal)

Anaerobic Metabolism

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

Anaerobic? So What?

Inadequate Cellular Oxygenation Inadequate Energy Production Anaerobic Metabolism Metabolic Failure Cell Death!

Lactic Acid Production Metabolic Acidosis

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

Muscle Anatomy

Contraction: Sliding Filaments image from: http://www.accessexcellence.com/AB/GG/muscle_Contract.html

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

Autonomic Nervous System Review… Quiz Time! Yeah!

Jeopardy Controls vegetative functions,exits the CNS at high in the neck and low in the back.

What is the parasympathetic nervous system?

Jeopardy The chief neurotransmitter of the sympathetic nervous system.

What is Norepinephrine?

Jeopardy The ‘cutesy’ name for the parasympathetic nervous system.

What is ‘Feed or Breed’?

Jeopardy Two types of parasympathetic receptors.

What is nicotinic (NMJ) and muscarinic (organs)?

Jeopardy Two types classes of sympathetic receptors.

What is alpha and beta?

Jeopardy The ‘cutesy name’ for the sympathetic nervous system.

What is ‘fight or flight’?

Jeopardy Stimulation of this receptor causes an increase in peripheral vasoconstriction.

What is alpha 1?

Jeopardy Stimulation of this receptor causes an increase in myocardial contractility.

What is beta 1?

Jeopardy Stimulation of this receptor causes an increase in bronchodilation.

What is beta 2?

Jeopardy Stimulation of this receptor causes a decrease in the sympathetic activation.

What is alpha 2?

Jeopardy Two types of parasympathetic receptors.

What is nicotinic (NMJ) and muscarinic (organs).

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

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

Changes in Afterload and Preload   fluid volume…   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.

Fluid  Must have adequate amounts of hemoglobin  Must have adequate intravascular volume

Maintenance of Fluid Volume  Renin-Angiotensin-Aldosterone system.

 Works through kidneys to regulate balance of Na + and water.

Renin-Angiotensin-Aldosterone &/Or  Plasma volume  [Na+] Detected by Via ACE (Angiotensin Converting Enzyme) Kidney (juxtaglomerular apparatus) Releases Renin Converts Angiotensin II… Angiotensin I… Angiotensinogen

Renin-Angiotensin-Aldosterone  vasoconstriction  PVR Angiotensin II…  thirst Adrenal cortex  ADH (anti-diuretic hormone) Releases  Fluid volume Aldosterone  BP!

 Na+ reabsorption

Hemostasis  The stoppage of bleeding.

 Three methods  Vascular constriction  Platelet plug formation  Coagulation

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

Fibrinolysis  Plasminogen  Tissue plasminogen activator (tPA)  Plasmin

Disseminated Intravascular Coagulation “A systemic thrombohemorrhagic disorder … with evidence of: 1) Procoagulant activation 2) Fibrinolytic activation 3) 4) 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 O 2 dependent on:  Adequate fio 2  Appropriate O 2 diffusion into bloodstream  Adequate number of RBCs  Proper tissue perfusion  Efficient hemoglobin ‘loading’

Fick Principle  Perfusion = Arterial O 2 Venous O 2 Content  Affected by: Content  Hemoglobin levels  circulation of RBCs  distance between alveoli and capillaries  pH and temperature

Onloading Oxygen in Lungs

oxyhemeglobin

pH 7.45

Remember: CO 2  [H + ] pH 7.4

•  •  pH shifts curve to left ‘onloading’ in lungs

deoxyhemeglobin Pressure

Offloading Oxygen in Tissues

oxyhemeglobin

pH 7.4

Remember: CO 2  [H + ] pH 7.35

deoxyhemeglobin Pressure

•  pH shifts curve to right •  ‘offloading’ to tissues

Causes of Inadequate Perfusion   Inadequate fluid volume  Hypovolemia  Inadequate pump  Inadequate preload  Poor contractility  Excessive afterload  Inadequate heart rate 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

Cellular Response to Shock  O 2 use  Tissue perfusion Impaired cellular metabolism Anaerobic metabolism  ATP synthesis  Na + Pump Function Stimulation of clotting cascade & inflammatory response  Intracellular Na + & water Impaired glucose usage   Cellular edema Vascular volume

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”

Cardiogenic Shock R.A.S.

Activation  CO  Catecholamine Release  Volume/ Preload Impaired myocardial function  Myocardial O 2 demand  SVR  Dyspnea  O 2 supply  Peripheral & pulmonary edema

Neurogenic Shock  Sympathetic Tone Or  Parasympathetic Tone  Tissue perfusion  Vascular Tone Massive Vasodilation  Cardiac Output  SVR & Preload

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.ht

m 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.h

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