CO and SVR Flashcards
1
Q
Def Mean circulatory filling pressure
A
pressure equalization when the heart is stopped
2
Q
Def Mean SYSTEMIC filling pressure
A
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
3
Q
Factor influencing the mean systemic filling pressure
A
- 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
4
Q
What point on the curve
A
Intersection of the curve: venous return x CO
5
Q
CO equation
A
SV x HR
6
Q
CO def
A
volume of blood pumped by the heart
* Normal = 6-8L/min
7
Q
Determinants of CO
A
- 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
8
Q
Effect of afterload on CO
A
- 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
9
Q
effect of HR on CO
A
- 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
10
Q
Effect of preload on CO
A
- incr EDV => activate Frank Starling mechanism => incr contractility => incr CO
- Beat to beat matching of venous return and CO
11
Q
Measurement of CO 4 methods
A
- 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
12
Q
What needs to happen w/ exercise
A
Incr CO
13
Q
Most important factor contributing to incr CO during exercise
A
HR
14
Q
Important determinants of CO during exercise
A
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
15
Q
Emotional stress pathophys
A
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
16
Q
Central control of CO w/ exercise
A
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
17
Q
Neurohormonal control of CO during exercise
A
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
18
Q
Explain mechanisms of arteriolar vasodilation and incr blood flow during exercise
A
- 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
19
Q
What determines O2 uptake during exercise
A
determined by HR and wall stress
o Preload and afterload
o incr O2 uptake => incr mitochondrial metabolic rate => incr ATP production
20
Q
Differentiate dynamic vs static exercise
A
- 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
21
Q
Exercise phenotype
A
- 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
22
Q
What causes variations in BP
A
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
23
Q
BP equation
A
CO x SVR
24
Q
BP is determined by
A
- 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
25
Equation MAP
syst BP - 2x diast BP/3
26
MAP def
average pressure throughout cardiac cycle
Approximation of arteriolar resistance
Not arithmetical mean of Syst BP and diast BP
Stable during exercise
27
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
28
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
29
Chronic control of BP
Renal-fluid volume mechanism
* Dominant force on long term control
* Pressure natriuresis/diuresis: incr BP => incr Na+ and H2O excretion
30
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
31
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
32
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
33
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
34
NO release stim by
adenosine, Ach and bradykinin
35
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)
36
BP with exercise
incr CO + systolic BP but stable mean BP
o Adrenergic decr in PVR
37
BP with stress
adrenergic response
o B stim: incr HR + vasodilation
o Prolonged ET1 response which impair vasodilation
38
Acute BP regulation
o Autonomic control: adrenergic and cholinergic activity
o Baroreflexes
o Local control of peripheral arteriolar tone: NO, adenosine, autonomic signals
39
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
40
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
41
Incr pulse pressure
incr SV => PDA, arteriovenous fistula, severe AI
Symp hyperactivity
Severe bradycardia
Hyperkinetic states: anemia, fever, high output states (hyperT4)
42
Decr pulse pressure
decr CO: LVOTO
Volume depletion
43
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)
44
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
45
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
46
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
47
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
48
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
49
Clinical appearance of seizures
Preictal period
Tonic/clonic limb motions, motor activity, chomping, hypersalivation
Postictal period >10min
Neurologic deficits
50
Clinical appearance of syncope
Opisthotonos
Motionless: relaxed or extended limbs
Able to stand after <1min
51
Seizure vs syncope
o Both: urination, defecation
o Generalized clonic mvts: may occur w any condition causing pancerebral hypotension/perfusion
52
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
53
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
54
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
