CO and SVR Flashcards
Def Mean circulatory filling pressure
pressure equalization when the heart is stopped
Def Mean SYSTEMIC filling pressure
pressure in systemic circulation after heart is stopped and isolated from pulmonary vasculature
- Almost equivalent because pulmonary circulation is 1/8 capacitance and 1/10 blood volume of systemic circulation
- Normal in dogs is 7mmHg => closer to normal venous pressure because much more blood into venous circulation
Factor influencing the mean systemic filling pressure
- Blood volume
o If blood volume incr => incr mean systemic filling pressure (incrRAP)
o Greater degree the system is filled => easier for blood to flow in the heart
o Higher difference btw mean systemic filling pressure and RAP => incr venous return
Pressure gradient for venous return - Atrial pressure
o incrRAP/LAP
decr venous return
incr CO - CO: matched to venous return with Starling law
o Atrial pressure => also matches venous return to CO
What point on the curve
Intersection of the curve: venous return x CO
CO equation
SV x HR
CO def
volume of blood pumped by the heart
* Normal = 6-8L/min
Determinants of CO
- Preload: LV volume at end of diastole
o LVEDP if normal compliance and pressure-volume relationship - Afterload: resistance against ejection of blood
o PVR, valve stenosis, Ao impedance
o Blood distending LV at end diastole - Contractility: capacity of myocardium to contract
o Independently of preload and afterload - HR: # of heart beat/min
Effect of afterload on CO
- Normal function: if normal BP => CO determined by ease of blood flow to arterioles
- decr afterload => ↑ CO
- incr afterload => initial compensatory mechanism to maintain SV
o Acute: stretch induced incr Ca2+ entry in myo¢
Acute failure possible if excessive acute incr afterload
o Chronic/long term: CO inversely proportional to BP/afterload incr
effect of HR on CO
- incr HR => incr CO and O2 uptake
o Until a certain point
o Dynamic exercise => for any HR => incr CO
Concomitant sympathetic stimulation => incr contractility
Peripheral vasodilation → ↓ afterload - Exceptions
o If tachycardia > 220bpm => decr diastolic filling time => decr CO
o Myocardial failure => lesser incr in HR can decr CO
Effect of preload on CO
- incr EDV => activate Frank Starling mechanism => incr contractility => incr CO
- Beat to beat matching of venous return and CO
Measurement of CO 4 methods
- Fick principle => accurate but invasive
o Arteriovenous difference of O2
o O2 uptake determined by spirometry
o CO = volume of blood needed to account for O2 uptake - Swan-Ganz KTerization: thermodilution method
o Measure rate of T˚ decr at tip of KT after injection of ice cold saline into central venous circulation - Angiography: depends on SV determination
o End diastolic – end systolic images - Doppler estimations: non invasive, not as accurate
o Area of MV orifice on 2D echo
o Mean velocity of blood flow across MV
What needs to happen w/ exercise
Incr CO
Most important factor contributing to incr CO during exercise
HR
Important determinants of CO during exercise
a) ↑ HR → most important factor that mediate incr CO
b) incr venous return => Frank starling law => incr contractility => incr SV
o Additional venous return may originate from redistribution of blood
o incr RAP => incr LV filling
o Tachycardia producing Brainbridge reflex → incrHR
Stimulated by incr venous return
Stretch receptors located in both sides of atria and venoatrial jcts
c) Afterload: systolic BP incr despite peripheral vasodilation
o Healthy heart can deal w hemodynamic changes
o Failing heart cannot cope w incr peripheral resistance
2nd to incr Ang II + other vasoconstrictors
Emotional stress pathophys
incr CO secondary to sympathetic stimulation
* decr SVR + incr splanchnic vasoconstriction
* incr myocardial O2 demand => from β and α adrenergic activity
* Secretion of epinephrine mostly => tachycardia => incr SV
o Stable BP
Central control of CO w/ exercise
Vasomotor center in brainstem => incr sympathetic stimulation (adrenergic drive)
1. Central command from cerebral cortex
o Crucial for static + dynamic exercise
2. Signal from exercising muscles
3. Signals from baroR
Cardiovascular control centers: insular cortex => hypothalamus => vasomotor centers => stimulate sympathetic and inhibits vagal tone
* Insular cortex
* Hypothalamus
* Nucleus solitarius
* Vagal nucleus
* Sympathetic vasomotor center
Neurohormonal control of CO during exercise
B-adrenergic R stimulation = basic to the tachycardia induced by exercise
* incr circulating catecholamines => major stimulus of tachycardia
* If B-adrenergic blockade => HR can still incr but to a lesser extent
o Competitive antagonism of B blocker by incr adrenergic drive
* β1 activation → positive inotrope, dromotrope, chronotrope, lusitrope
* β2 activation → ↓ afterload/PVR
o Systolic BP ↑ and diastolic BP ↓/same
Explain mechanisms of arteriolar vasodilation and incr blood flow during exercise
- Autonomic + local metabolic factors
o Vasodilatory metabolites: adenosine, protons, CO2, K+ - Normally, resting vascular tone is mediated by A vasoconstriction
o incr venous return => low pressure R => decr peripheral vasoconstriction - ↑ arterial pressure → vasoconstriction of arterioles and small arteries in most tissues
o Except brain and active muscles
o Venous contraction: ↑ systemic filling pressures → ↑ venous return to RA → ↑ CO
o Arteriolar contraction:
↑ force of flow to tissues
Stretch vessel walls → release local vasodilators → ↑ total muscle blood flow - Working muscles: local vasodilatory effects
What determines O2 uptake during exercise
determined by HR and wall stress
o Preload and afterload
o incr O2 uptake => incr mitochondrial metabolic rate => incr ATP production
Differentiate dynamic vs static exercise
- Dynamic exercise = aerobic exercise
o Regular muscular activity against light load
HR incr => withdrawal of vagal inhibition => B adrenergic stimulation => incr contractility => incr SV
CO incr because HR + SV incr
Lower ↑ in systolic BP → 50-70mmHg
o Concurrent splanchnic vasoconstriction => redistribution of blood from abdominal viscera to exercising muscles + heart - Static exercise
o Modest incr in HR, stable SV => incr CO is proportional to incr in HR
o Higher ↑ in systolic BP → 20-40 mmHg
Exercise phenotype
- With repetitive exercise training
o decr resting HR and HR response to submaximal exercise
Imbalance btw sympathetic and parasympathetic neural stimulation to the heart
Intrinsic PM currents
o Rapid recovery of resting HR after exercise
NO acts presynaptically to incr Ach release => antagonize sympathetic nervous system
What causes variations in BP
o Age: incr diastolic & systolic BP w age
decr Ao elasticity => incr diastolic BP
No end systolic recoil maintaining BP
o Body condition: obesity is a predisposing factor for hypertension
o Gender
o Breed
BP equation
CO x SVR
BP is determined by
- Systemic vascular resistance (SVR):
o Arteriolar resistance => major determinant at rest
Poiseuille’s law : blood vessel diameter = key determinant of resistance
Resistance incr rapidly in small arteries, greatest in arterioles
o Vasoconstriction stimulated by:
symp system
Adrenal release of Epi/NE => stimulates cardiac and vascular muscle ¢
Ang II => incr NE release
CO = major determinant during exercise
Equation MAP
syst BP - 2x diast BP/3
MAP def
average pressure throughout cardiac cycle
Approximation of arteriolar resistance
Not arithmetical mean of Syst BP and diast BP
Stable during exercise
acute autonomic control BP
- Acutely modify BP + HR => cardiovascular homeostasis
- Baroreceptors
o Stretch R in carotid sinus and Ao arch => vagus/glossopharyngeal nerves => signals to brainstem vasomotor center => nucleus solitarius => adrenergic/cholinergic vagal systems
decr BP => decr impulses to vasomotor center => incr symp efferent => vasoconstriction + incr HR => incr BP
incr BP => incr neuronal traffic to vasomotor center => decr symp outflow + incr vagal tone => decr HR, contractility, CO => decr BP - Cardiopulmonary receptors: senses stretch in atria, ventricles, PAs
o Respond to volume alteration on venous side
o incr blood volume => vagal afferent fibers => vasomotor centers => decr symp outflow => decr renin release - Bainbridge reflex
o Mediated by stretch R at jct of LA and PVs
o incr atrial pressure => incr HR
Acute hormonal control of BP
RAAS
- Antidiuretic hormone (ADH)
o Secreted in posterior pituitary gland
o Dehydration => incr osmolality => osmoR in hypothalamus => ADH secretion => V2 R in collecting duct => incr H2O reabsorption
o decr blood volume => stretch R in atria => ADH => V1 R => vasoconstriction
o incr blood volume => decr ADH secretion - Atrial natriuretic peptide (ANP)
o incr blood volume => atrial distension => ANP release from storage granules
SM¢ => promote vasodilation through cGMP - Inhibit Ang II mediated vasoconstriction
SA node => facilitate release of Ach => vagal induced bradycardia
Kidneys => direct diuretic effect + inhibition of aldosterone/renin secretion - Bind to renal R in nephrons =>
o Vasodilation of afferent arteriole/vasoconstriction of efferent => incr GFR
o Relax mesangial ¢ => incr glomerular permeability - Catecholamines: acute response
o NE released in terminal neurons = locally active => promotes vasoconstriction
o decr BP => reflex B stimulation => release renin
Chronic control of BP
Renal-fluid volume mechanism
* Dominant force on long term control
* Pressure natriuresis/diuresis: incr BP => incr Na+ and H2O excretion
Pathophys of hypertension
- Na+ retention: incr intra¢ Na+
o incr sensitivity to catecholamines + AngII
o Predispose to incr arteriolar tone - Blood viscosity: related to
o Hct
o Plasma viscosity
o ¢ deformability - Atherosclerosis/arteriosclerosis => decr luminal diameter + decr elasticity => incr vascular resistance
- SM¢ stretch => incr Ca2+ entry via stretch activated channel => incr SM¢ tone
o incr vascular tone => reflex contraction of SM¢ w hypertension
Offset tendency to split arteriole w incr intraluminal pressure
o incr sensitivity to vasopressors - Fibroblast & platelet-derived GF produced by endothelial ¢ and platelets => mitogenic for SM¢
- Nephrosclerosis
o Hypoxic nephrons 2nd to afferent arteriole vasoconstriction => RAAS activation
o decr efficiency to excrete Na+ and H2O - Obese dogs: incr BP
o incr baroreflex sensitivity
o Blunted natriuretic responses
Clinical consequence of hypertension
target organs
* Cardiovascular system
o Vascular medial hypertrophy/hyperplasia (incr arterial SM work)
Induced by vasopressors, incr cytosolic Ca2+, autoregulatory vasospasm
o Intimal damages: atherosclerosis + arteriosclerosis
Major arteries incr thick, stiff
- Eyes: can cause blindness
o Retinal hemorrhage, detachment, hyphema - Kidneys
o PUPD: from pressure diuresis or primary KD
o Glomerular damage: proteinuria, renal failure - Neurovascular systems
o Neurovascular/cerebrovascular accidents: arteriosclerosis, vasospasm, infarcts, hemorrhage
NO synthesis
- Synthetized endogenously from L arginine + O2
o By NO synthase isoenzymes (eNOS) in vascular endothelium
o Paracrine action
o psymp activation - If endothelium damaged → endothelin is released leading to vasoconstriction
Intracell signaling NO
- Activates guanylate cyclase => increases cGMP => inhibit MLCK → vasodilation
o Potent vasodilator
o Inhibitor of platelet activation
o Inhibitor of vascular smooth muscle cell proliferation
o Rapidly inactivated by phosphodiesterase, particularly PDE-5 isoenzyme
NO release stim by
adenosine, Ach and bradykinin
Mean BP
= not mean of diastolic and systolic BP because heart is spending diastole is 2x longer vs systole
Mean BP = CO x PVR
= diatolic BP + 1/3 (systolic BP – diastolic BP)
BP with exercise
incr CO + systolic BP but stable mean BP
o Adrenergic decr in PVR
BP with stress
adrenergic response
o B stim: incr HR + vasodilation
o Prolonged ET1 response which impair vasodilation
Acute BP regulation
o Autonomic control: adrenergic and cholinergic activity
o Baroreflexes
o Local control of peripheral arteriolar tone: NO, adenosine, autonomic signals
Long term regulation BP
o Neurohumoral regulation of blood volume
Catecholamines: Epi, NE
Antidiuretic hormone (ADH)
Atrial natriuretic peptide: via stretch R in atria
* Vasodilation of vascular SM¢ via cGMP
* SA node: facilitate Ach release => vagally mediated bradycardia
* Diuretic actions: direct effect on kidney + inhibition of aldosterone secretion
o Renal factors: RAAS (see question #24 for details)
Renin release => Ang II = powerful vasoconstrictor
* 3 major stimuli: incr B1 stimulation, decr renal artery P, decr tubular reabsorption of Na+
* Inhibited by negative feedback of Ang II
Pulse pressure
- Difference btwn systolic and diastolic BP
- Affected by SV or arterial compliance
- Progressively incr in the arterial tree => reflection of the pulse wave
Incr pulse pressure
incr SV => PDA, arteriovenous fistula, severe AI
Symp hyperactivity
Severe bradycardia
Hyperkinetic states: anemia, fever, high output states (hyperT4)
Decr pulse pressure
decr CO: LVOTO
Volume depletion
Major mechanisms controlling PVR
- Vasoconstrictor receptor => incr intrac Ca2+ => promote vasoconstriction
o Respond to agonist from neurogenic, neurohumoral and endothelial systems
A1-adrenergic R: NE released from terminal neurons in response to adrenergic stim
Ang II: major vasoconstrictor + incr NE release
ET1: vasoconstrictive peptide released from damaged endothelium - Cyclic nucleotide vasodilatory system
o Inhibit myosin light chain kinase (that activates vascular contraction)
o cAMP: from B adrenergic stim via B2R in arterioles
o cGMP: from NO messenger system - Endothelial control
o Healthy endothelium: release NO
Other vasodilators: prostacyclin, endothelium derived hyperpolarizing factor
o Damaged endothelium: release ET1
Low physiologic [ET1] => vasodilation via ETB => NO release
High pathologic [ET1] => vasoconstriction via ETA
o Hypoxia/thrombin/O2 free radicals => decr vasodilators + incr ET1 release
o Shear stress: both physiologic (NO) and pathologic stimuli (ET1)
Myogenic properties and effect on BP
- incr transmural pressure (hypertension or incr BP) => vasoconstriction => further incr BP
- incr wall tension to avoid tendency of splitting the wall
BP Autoregulation in regional circulation
- Brain/heart/kidneys: continuous perfusion relatively independent of circulatory control mechanisms
o Maintenance of blood flow = vital
o Lower limits:
Heart: <50mmHg
Brain: <73mmHg
Kidneys: incr efferent arteriole resistance to maintain GFR
Effect of age on BP
- Systolic BP depends on aortic compliance + SV
o Mid systole: expansion od Ao
o End systole, start of diastole: elastic recoil that maintain diastolic BP - With age => decr aortic elacticity => loss of buffer fct => decr diastolic BP
o Abrupt incr and decr in pulse wave
Def syncope
transient loss of consciousness w spontaneous recovery
o Episodic weakness, near-syncope, pre-syncope: sudden generalized weakness, ataxia, collapse
o Cessation of blood flow for >7-10sec
4 major pathophys mechanism for vasovagal syncope
o Cardiogenic dysfct
Bradyarrhythmias: heart block, sinus bradycardia, SSS
Tachyarrhythmias: SVT, VT
Cardiac underfilling: tamponade, masses
decr ventricular ejection: SAS, PS, HCM, volume depletion
o Hypotensive disorders
DCM
decr blood volume or BP
Drugs
o Alterations in blood constituents
Hypoglycemia, hypoxia, anemia, hyperviscosity
o Neurologic
Obstruction to cerebral flow => TE, arteriosclerosis
Clinical appearance of seizures
Preictal period
Tonic/clonic limb motions, motor activity, chomping, hypersalivation
Postictal period >10min
Neurologic deficits
Clinical appearance of syncope
Opisthotonos
Motionless: relaxed or extended limbs
Able to stand after <1min
Seizure vs syncope
o Both: urination, defecation
o Generalized clonic mvts: may occur w any condition causing pancerebral hypotension/perfusion
MOA vasovagal reflex
Carotid sinus hypersensitivity, postural hypotension, micturition/defecation induced
Hypotension/hypovolemia = precipitating event
* Sudden symp tone withdrawal + incr psymp tone => decr HR and vasomotor tone
* Cardiac mechanoR stimulation
o Hypotension => adrenergic stim => incr contractility => decr blood volume in ventricle => stim myocardial C fibers (mechanoR) => inhibit symp tone + stim psymp
o Hypotension + bradycardia => decr cerebral blood flow
* Similar syndrome described in Boxers
Tx vasovaga; syncope
B blockers: act earlier in reflex arc => prevent initial ∑ release + effect on cardiac mechanoR
Anticholinergic drugs (propanthelin): act on bradycardia but not hypotension
Cough drop syndrome
- One of most common cause of syncope in dogs
- Coughing induce:
o incr intracranial pressure => decr cerebral blood flow
o incr intrathoracic pressure => decr venous return =>decr CO
o Reflex bradycardia and vasodilation
