PH402 Regulation of Cardiac Output

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PH402 Regulation of Cardiac Output

• Chris Hague, PhD
• chague_at_u.washington.edu
• Technical Advisor Seth Goldenberg, PhD

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References

• Brodys Human Pharmacology, 4th Edition
• Guyton Human Physiology
• http//www.colorado.edu/kines/Class/IPHY3430-200/0
  9cardio.html
• http//www.edcenter.sdsu.edu/cso/paper.html

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Outline

• 1. Function and Anatomy of the Heart
• 2. Cardiac Output, Afterload and Preload
• 3. Excitation-contraction coupling
• 4. Frank-Starling and Venous Return
• 5. Autonomic Regulation of Cardiac Output

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Role of the Heart
- pumps blood around the body
- left heart pumps oxygenated blood
- right heart pumps deoxygenated blood
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Anatomy of the Heart
Pulmonary Valve
Right Atrium
Left Atrium
Mitral Valve
Tricuspid Valve
Aortic Valve
Right Ventricle
Left Ventricle
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The Cardiac Cycle

• events that occur from beginning of one heartbeat
  to beginning of next heartbeat
• consists of 2 periods
• Diastole relaxation, heart fills with blood (BP
  80 mm Hg)
• Systole contraction, blood is ejected (BP 120
  mm Hg)

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Diastole

• venous filling of atria, A-V valve opens
• 75 flow-through to ventricles
• Atrial Priming 25 increase in ventricular
  filling
• A-V valve closes

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Systole

• ventricular filling, increased pressure
• isometric contraction aortic/pulmonary valve
  opens
• period of ejection 70 fast,
  30 slow
• ventricular relaxation
• aortic/pulmonary valves close

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What is Cardiac Output?
Cardiac output Stroke Volume X Heart Rate
OR
CO SV x HR

• Stroke Volume blood volume ejected by
  ventricles/beat
• Heart Rate heart beats/min

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Preload/Afterload

• determinants of stroke volume
• Preload
• tension on ventricular muscle before contraction
• determined by left ventricular end diastolic
  volume
• Afterload
• pressure against which ventricles pump blood
• determined by total peripheral resistance

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Excitation-Contraction Coupling

• generation of rhythmical electrical impulses
• sinus (or sinoatrial) node
• propagation of impulses throughout the heart
• internodal pathways
• A-V node
• A-V bundle
• Purkinje fibers

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Generation of cardiac rhythmicity

• Sinus node
• small specialized muscle in right atrium
• controls heart rate
• spontaneous action potential

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Cardiac Electrophysiology
Na
Ca2
Na
Ca2
K
K
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Ion channel conformational states

• 3 states
• resting closed, can be opened
• activated open and ions moving
• inactivated closed and can not be opened

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Spontaneous Action Potentials

• 2 ion channels regulate rhythmicity
• slow Ca channels phase O
• K channels phase 3
• membrane leakiness phase 4

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Transmission of Cardiac Impulses

• Internodal pathways
• spread current around atrial muscle
• A-V node
• separates atria and ventricles
• delays spread of signal to ventricles
• has spontaneous activity (ectopic pacemaker)
• Purkinje fibers
• spreads impulse around ventricles

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Non-spontaneous Action Potential

• 3 ion channels regulate firing
• fast Na channels phases 0 1
• slow Ca channels phase 2
• K channels phases 3 4

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Cardiomyocyte Contraction

• increased Ca2i through Ca2 channels
• Ca2 spread by transverse T-tubules
• opens ryanodine receptors on sarcoplasmic
  reticulum
• Ca2 induced Ca2 release

• Ca2 binds to troponin-tropomyosin
• actin-myosin filament movement

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Factors affecting Cardiac Output

• Frank-Starling Mechanism
• Autonomic Inputs
• sympathetic nervous system
• parasympathetic nervous system
• Cardiovascular disease

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Frank-Starling Mechanism

• venous return
• increased cardiomyocyte contractility
• increased stroke volume

within physiological limits, the heart pumps all
the blood it receives without allowing excessing
damming of blood in the veins
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Autonomic Regulation of Cardiac Output

• Parasympathetic Nervous System
• decreases HR and SV
• dominant at rest
• Sympathetic Nervous System
• increases HR and SV
• dominant during exercise/stress

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Autonomic Nervous Systemschematic
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Parasympathetic Effects

• Vagal nerves release acetylcholine at SA and A-V
  nodes
• stimulates muscarinic receptors
• increased K channel opening
• decreased sinus node rhythm
• decreased A-V node transmission
• ventricular escape

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Sympathetic Effects

• Sympathetic nerves release norepinephrine
  throughout heart
• stimulates adrenergic receptors
• increased Ca and Na channel opening
• increased SA node rhythm
• increased A-V node transmission
• increased force of atrial and ventricular
  contraction

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Baroreceptor Reflex

• rapid control of CVS function
• sensory baroreceptors in carotid sinus and aortic
  arch detect BP changes
• increased BP detected, increased vagal firing,
  decreased CO
• decreased BP detected, increased sympathetic
  firing, increased CO

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Renin-Angiotensin System

• decreased BP causes release of renin from
  juxtaglomerular cells of kidney into blood
• renin cleaves angiotensin to angiotensin I
• angiotensin converting enzyme (ACE) converts
  Ang-I to Ang-II

• Ang-II increases plasma volume and BP, increases
  CO.

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Diseases affecting cardiac output

• atherosclerosis increased TPR, increased
  afterload
• coronary artery disease decreased cardiac O2
  supply
• congestive heart failure decreased stroke volume
• stroke
• renal disease
• diabetes