CO and SVR

Question 1

Def Mean circulatory filling pressure

Answer 1

pressure equalization when the heart is stopped

Question 2

Def Mean SYSTEMIC filling pressure

Answer 2

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

Question 3

Factor influencing the mean systemic filling pressure

Answer 3

• 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

Question 4

What point on the curve

Answer 4

Intersection of the curve: venous return x CO

Question 5

CO equation

Answer 5

SV x HR

Question 6

CO def

Answer 6

volume of blood pumped by the heart
* Normal = 6-8L/min

Question 7

Determinants of CO

Answer 7

• 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

Question 8

Effect of afterload on CO

Answer 8

• 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

Question 9

effect of HR on CO

Answer 9

• 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

Question 10

Effect of preload on CO

Answer 10

• incr EDV => activate Frank Starling mechanism => incr contractility => incr CO
• Beat to beat matching of venous return and CO

Question 11

Measurement of CO 4 methods

Answer 11

• 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

Question 12

What needs to happen w/ exercise

Answer 12

Incr CO

Question 13

Most important factor contributing to incr CO during exercise

Answer 13

HR

Question 14

Important determinants of CO during exercise

Answer 14

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

Question 15

Emotional stress pathophys

Answer 15

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

Question 16

Central control of CO w/ exercise

Answer 16

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

Question 17

Neurohormonal control of CO during exercise

Answer 17

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

Question 18

Explain mechanisms of arteriolar vasodilation and incr blood flow during exercise

Answer 18

• 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

Question 19

What determines O2 uptake during exercise

Answer 19

determined by HR and wall stress
o Preload and afterload
o incr O2 uptake => incr mitochondrial metabolic rate => incr ATP production

Question 20

Differentiate dynamic vs static exercise

Answer 20

• 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

Question 21

Exercise phenotype

Answer 21

• 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

Question 22

What causes variations in BP

Answer 22

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

Question 23

BP equation

Answer 23

CO x SVR

Question 24

BP is determined by

Answer 24

• 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

Question 25

Equation MAP

Answer 25

syst BP - 2x diast BP/3

Question 26

MAP def

Answer 26

average pressure throughout cardiac cycle
 Approximation of arteriolar resistance
 Not arithmetical mean of Syst BP and diast BP
 Stable during exercise

Question 27

acute autonomic control BP

Answer 27

• 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

Question 28

Acute hormonal control of BP

Answer 28

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

Question 29

Chronic control of BP

Answer 29

Renal-fluid volume mechanism
* Dominant force on long term control
* Pressure natriuresis/diuresis: incr BP => incr Na+ and H2O excretion

Question 30

Pathophys of hypertension

Answer 30

• 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

Question 31

Clinical consequence of hypertension

Answer 31

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

Question 32

NO synthesis

Answer 32

• 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

Question 33

Intracell signaling NO

Answer 33

• 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

Question 34

NO release stim by

Answer 34

adenosine, Ach and bradykinin

Question 35

Mean BP

Answer 35

= 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)

Question 36

BP with exercise

Answer 36

incr CO + systolic BP but stable mean BP
o Adrenergic decr in PVR

Question 37

BP with stress

Answer 37

adrenergic response
o B stim: incr HR + vasodilation
o Prolonged ET1 response which impair vasodilation

Question 38

Acute BP regulation

Answer 38

o Autonomic control: adrenergic and cholinergic activity
o Baroreflexes
o Local control of peripheral arteriolar tone: NO, adenosine, autonomic signals

Question 39

Long term regulation BP

Answer 39

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

Question 40

Pulse pressure

Answer 40

• Difference btwn systolic and diastolic BP
• Affected by SV or arterial compliance
• Progressively incr in the arterial tree => reflection of the pulse wave

Question 41

Incr pulse pressure

Answer 41

 incr SV => PDA, arteriovenous fistula, severe AI
 Symp hyperactivity
 Severe bradycardia
 Hyperkinetic states: anemia, fever, high output states (hyperT4)

Question 42

Decr pulse pressure

Answer 42

 decr CO: LVOTO
 Volume depletion

Question 43

Major mechanisms controlling PVR

Answer 43

• 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)

Question 44

Myogenic properties and effect on BP

Answer 44

• incr transmural pressure (hypertension or incr BP) => vasoconstriction => further incr BP
• incr wall tension to avoid tendency of splitting the wall

Question 45

BP Autoregulation in regional circulation

Answer 45

• 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

Question 46

Effect of age on BP

Answer 46

• 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

Question 47

Def syncope

Answer 47

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

Question 48

4 major pathophys mechanism for vasovagal syncope

Answer 48

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

Question 49

Clinical appearance of seizures

Answer 49

 Preictal period
 Tonic/clonic limb motions, motor activity, chomping, hypersalivation
 Postictal period >10min
 Neurologic deficits

Question 50

Clinical appearance of syncope

Answer 50

 Opisthotonos
 Motionless: relaxed or extended limbs
 Able to stand after <1min

Question 51

Seizure vs syncope

Answer 51

o Both: urination, defecation
o Generalized clonic mvts: may occur w any condition causing pancerebral hypotension/perfusion

Question 52

MOA vasovagal reflex

Answer 52

 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

Question 53

Tx vasovaga; syncope

Answer 53

 B blockers: act earlier in reflex arc => prevent initial ∑ release + effect on cardiac mechanoR
 Anticholinergic drugs (propanthelin): act on bradycardia but not hypotension

Question 54

Cough drop syndrome

Answer 54

• 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