Cardiovascular anatomy, physiology

• Coronary artery anatomy
• Right coronary artery (RCA):
• -SA and AV nodes are usually supplied by RCA
• → Acute marginal artery: supplies right ventricle

• →Posterior descending/interventricular artery (PD): supplies posterior 1/3 of interventricular septum and posterior walls of ventricles
• -Right dominant circulation: 85%; PD arises from RCA

• Left main coronary artery (LCA):
• →Left circumflex coronary artery (LCX): supplies the lateral and posterior walls of left ventricle
•      →LCX → left marginal artery
•      →Left dominant circulation: 8% (PD artery arises from LCX
• → Left anterior descending artery (LAD): supplies anterior 2/3 of interventricular septum, anterior papillary muscle, and anterior surface of LV

• Right-dominant circulation: 85% = PD arises from RCA
• Left-dominant circulation: 8% = PD arises from LCX
• Codominant circulation: 7% = PD arises from both LCX and RCA

LAD

• Diastole
• Pathological tachycardia (Wolff-Parkinson-White syndrome; >250bpm) is problematic due to decreased filling time
• Diastolic refilling time sets the limit for maximam useful heart rate

• The most posterior part of the heart is the left atrium
• → enlargement: dysphagia (due to compression of the esophagus); hoarseness (due to compression of the left recurrent laryngeal nerve)

• TEE is useful for diagnosing:
• -left atrial enlargemnet
• -aortic dissection
• -thoracic aortic aneurysm
• -vegetation on valves

• CO = stroke volume (SV) × heart rate (SV)
• 

• 
• MAP = 2/3 Diastolic pressure + 1/3 Systolic pressure

• Pulse pressure = systolic pressure - diastolic pressure
• Pulse pressure is proportional to stroke volume

• Early stages of exercise: CO is maintained by ↑ HR and ↑ SV
• Late stages of exercise: CO is maintained by ↑ HR only (SV plateaus)

• **SV CAP
• -Stroke Volume affected by Contractility
• -Afterload
• -Preload

• Stroke volume increase with:
• - ↑ preload

• - ↓ afterload
• - ↑ contractility

• Contractility (and SV) increase with:
• -Catecholamines (↑ activity of Ca²⁺ pump in sarcoplasmic reticulum)
• -↑ intracellular Ca²⁺
• -↓ extracellular Na⁺ (↓ activity of Na⁺/Ca²⁺ exchanger)
• -Digitalis (blocks Na⁺/K⁺ pump → ↑ intracellular Na⁺ → ↓ Na⁺/Ca²⁺ exchanger activity → ↑ intracellular Ca²⁺)

• Contractility (and SV) decrease with:
• -β₁-blockade (↓ cAMP)
• -Heart failure (systolic dysfunction)
• -Acidosis
• -Hypoxia/hypercapnea (↓ P_O2/↑ P_CO2)
• -Non-dihydropyridine Ca²⁺ channel blockers

• ↑SV in:
• -Anxiety
• -exercise
• -pregnancy

A failing heart has ↓ SV

• ↑ afterload (proportional to arterial pressure)
• ↑ contractility
• ↑ heart rate
• ↑ heart size (↑ wall tension)

• Preload = ventricular EDV
• Afterload = mean arterial pressure (proportional to peripheral resistance)
• *VEnodilators (e.g., nitroglycerin) ↓ prEload
• *VAsodilators (e.g.e, hydrAlazine) ↓ Afterload (arterial)

• Preload ↑ with:
• -Exercise (slightly)

• - ↑ blood volume (e.g., overtransfusion)
• - Excitement (↑ sympathetic activity)

• Force of contraction is proportional to end-diastolic length of cardiac muscle fiber (preload)
• ↑ contractility with sympathetic stimulation, catecholamines, digoxin
• ↓ contractility with loss of myocardium (MI), β-blockers, calcium channel blockers
• 

• 
• EF is an index of ventricular contractility
• EF is normally ≥ 55%
• EF is decreased in systolic heart failure

• ΔP = Q × R
• (similar to Ohm's law: ΔV= I × R)
• Pressure gradient drives flow from high pressure to low pressure

• Resistance = driving pressure/ flow
• 
• -Directly proportional to the viscosity of the fluid and length of the vessel
• -Inversely proportional to the radius to the 4th power

• Total resistance of vessels in series = R₁ + R₂ + R₃...
• Total resistance of vessels in parallel = 1/R₁ + 1/R₂ + 1/R₃...
• Arterioles account for most of total peripheral resistance → regulate capillary flow

Viscosity (μ) depends mostly on hematocrit

• Viscosity ↑ in:
• -Polycythemia
• -Hyperproteinemic states (e.g., multiple myeloma)
• -Hereditary spherocytosis

• Viscosity ↓ in:
• - anemia

• Operating point of normal heart
• Cardiac output - venous return

• + inotropy
• ↑ blood volume (venous return)
• 

• Venous return is "normal"
• decreased inotropic state
• 

• 1. Isovolumetric contraction: period between mitral valve closure and aortic valve opening; period of highest O₂ consumption
• 2. Systolic ejection: period between aortic valve opening and lcosing
• 3. Isovolumetric relaxation: period between aortic valve closing and mitral valve opening
• 4. Rapid filing: period just after mitral valve opening
• 5. Reduced filling: period just before mitral valve closure

• S1: mitral and tricuspid valve closure; loudest at mitral area
• S2: aortic and pulmonary valve closure; loudest at left sternal border
• S3: in early diastole during rapid ventricular filling phase
• -Associated with ↑ filling pressures (e.g., mitral regurgitation, CHF)
• -More common in dilated ventricles (but normal in children and pregnant women)
• S4: "atrial kick" in late diastole
• -High atrail pressure
• -Associated with ventricular hypertrophy
• -Left atrium push against stiff LV wall

• a wave: atrial contraction
• c wave: RV contraction (closed tricuspid valve bulging into atrium)
• x descent: atrial relaxation and downward displacement of closed tricuspid valve during ventricular contraction
• v wave: ↑ right atrial pressure due to filling against closed tricuspid valve
• y descent: blood flow from RA to RV

• Normal splitting
• Wide splitting
• Fixed splitting
• Paradoxical splitting

• Normal splitting
• Inspiration → drop in intrathoracic pressure → ↑ venous return to the RV → increased RV stroke volume → ↑ RV ejection time → delayed closure of pulmonic valve

↓ pulmonary impedance (↑ capacity of the pulmonary circulation) also occurs during inspiration, which contributes to delayed closure of pulmonic valve

• Wide splitting
• Seen in conditions that delay RV emptying (pulmonic stenosis, right bundle branch block)
• Delay in RV emptying causes delayed pulmonic sound (regardless of breath)
• An exaggeration of normal splitting

• Fixed splitting
• Seen in ASD
• ASD → left-to-right shunt → ↑ RA and RV volumes → ↑ flow through pulmonic valve such that, regardless of breath, pulmonic closure is greatly delayed

• Paradoxical splitting
• Seen in conditions that delay LV emptying (aortic stenosis, left bundle branch block)
• Normal order of valve closure is reserved so that P2 sound occurs before delayed A2 sound
• On inspiration, P2 closes later and moves closer to A2, thereby "paradoxically" eliminating the split

• Systolic murmur:
• -Aortic stenosis
• -Flow murmur
• -Aortic valve sclerosis

• Systolic ejection murmur:
• -Pulmonic stenosis
• -Flow murmur (e.g., ASD, PDA)

• Diastolic murmur:
• -Aortic regurgitation
• -Pulmonic regurgitation

• Systolic murmur:
• -Hypertrophic cardiomyopathy

• Pansystsolic murmur:
• -Tricuspid regurgitation
• -Ventricular septal defect

• Diastolic murmur:
• -Tricuspid stenosis
• -Atrial septal defect

• Systolic murmur:
• -Mitral regurgitation

• Diastolic murmur:
• -Mitral stenosis

• Inspiration: ↑ intensity of right heart sounds
• Expiration: ↑ intensity of left heart sounds
• Hand grip (↑ systemic vascular resistance): 
• -↑ intensity of MR, AR, VSD, MVP mumurs
• -↓ intensity of AS, hypertrophic cardiomyopathy murmurs
• Valsalva (↓ venous return): 
• -↓ intensity of most murmurs
• -↑ intensity of MVP, hypertrophic cardiomyopathy murmurs
• Rapid squatting (↑ venous return, ↑ preload, ↑ afterload with prolonged squatting):
• -↓ intensity of MVP, hypertrophic cardiomyopathy murmurs

• aortic/pulmonic stenosis
• mitral/tricuspid regurgitation
• ventricular septal defect

aortic/pulmonic regurgitation, mitral/tricuspid stenosis

• Cardiac myoccytes, bundle of His, Purkinje fibers
• Phase 0: rapid upstroke
• Phase 1: initial repolarization
• Phase 2: plateau
• Phase 3: rapid repolarization
• Phase 4: resting potential

• Phase 0: voltage gated Na⁺ channels open
• Phase 1: inactivation of voltage-gated Na⁺ channels; voltage-gated K⁺ channels begin to open
• Phase 2: Ca²⁺ influx through voltage-gated Ca²⁺ channels balances K⁺ efflux; Ca²⁺ influx triggers Ca²⁺ released from SR and myocyte contracts
• Phase 3: massive K⁺ efflux due to opening of voltage-gated slow K⁺ channels and closure of voltage gated Ca²⁺ channels
• Phase 4: high K⁺ permeability through K⁺ channels

• Cardiac AP has plateau, due to Ca²⁺ influx and K⁺ efflux
• Myocyte contraction occurs due to Ca²⁺-induced Ca²⁺ release from the sarcoplasmic reticulum
• Cardiac nodal cells spontaneously depolarize during diastole resulting in automaticity due to I_fchannels ("funny current" channels responsible for a slow, mixed Na⁺/K⁺ inward current)
• Cardiac myocytes are electrically coupled to each other by gap junctions

• Occurs in the SA and AV nodes
• Phase 0: upstroke is due to voltage gated Ca2+ channels
• -Fast voltage-gated Na+ channels are permanently inactivated because of the less negative resting voltage of these cells
• -slow conduction velocity; used by AV node to prolong transmission from atria to ventricles
• Phase 2: plateau is absent
• Phase 3: inactivation of the Ca2+ channels and ↑ activation of K+ channels → ↑ K+ efflux
• Phase 4: slow diastolic depolarization
• -membrane potential spontaneously depolarizes as Na+ conductance ↑ (I_f different from I_Na)
• -Automaticity of SA and AV nodes
• -Slope of phase 4 in SA node determines HR
• -ACh/adenosine ↓ the rate of diastolic depolarization and ↓ HR
• -Catecholamines ↑ depolarization and ↑ HR
• Sympathetic stimulation ↑ the chance that I_f channels are open and thus ↑ HR

Purkinje > atria > ventricles > AV node

• SA node → atria → AV node → common bundle → bundle branches → Purkinje fibers → ventricles
• SA node "pacemaker" inherent dominace with slow phase of upstroke
• AV node: 100-msec delay; allows time for ventricular filling

Conduction system

• ANP is released from atrial myocytes in response to ↑ blood volume and atrial pressure
• Causes generalized vascular relaxation
• ↓ Na⁺ reabsorption at the medullary collecting tubule
• Constricts efferent renal arterioles and dilates afferent arterioles (cGMP mediated)
• Promotes diuresis and contributes to "escape from aldosterone" mechanism

• Receptors:
• -Aortic arch: transmits via vagus nerve to solitary nucleus of medulla (responds only to ↑BP)
• -Carotid sinus: transmits via glossopharyngeal nerve to solitary nucleus of medulla (reponds to ↓ and ↑ in BP)

• Hypotension → ↓ arterial pressure → ↓ stretch → ↓ afferent baroreceptor firing → ↑ efferent sympathetic firing and ↓ efferent parasympathetic stimulation → vasoconstriction, ↑ HR, ↑ contractility, ↑ BP
• -Important in the response to severe hemorrhage

Carotid massage: ↑ pressure on carotid artery → ↑ stretch → ↑ afferent baroreceptor firing → ↓ HR

• Cushing reaction: triad of hypertension, bradycardia, respiratory depression
• -↑ intracranial pressure constricts arterioles → cerebral ischemia and reflex sympathetic increase in perfusion pressure (hypertension) → ↑ stretch → reflex baroreceptor induced-bradycardia

• Peripheral: carotid and aortic bodies
• -Stimulated by ↓ P_O2 (<60mmHg), ↑ P_CO2, and ↓ pH of blood

• Central: 
• -Stimulated by changes in pH and P_CO2 of brain interstitial fluid; which in turn are influenced by arterial CO₂
• -Do NOT directly respond to P_O2

• Right Atrium: <5
• Right Ventricle: 25/5
• Pulmonary Artery: 25/10
• PCWP: <12 (good approximation of left atrial pressure)
• **In mitral stenosis, PCWP > LV diastolic pressure
• Left atrium: <12
• Left ventricle: 130/10
• Aorta: 130/90

• Lung: organ with largest blood flow (100% CO)
• Liver: largest share of systemic CO
• Kidney: highest blood flow per gram of tissue
• Heart: largest arteriovenous O₂ difference because O₂ extraction is~80%
• -↑O₂ demand is met by ↑ coronary blood flow, not by ↑ extraction of O₂

• Heart: local metabolites (vasodilatory) - CO₂, adenosine, NO
• Brain: local metabolites (vasodilatory) - CO₂ (pH)
• Kidneys: Myogenic and tubuloglomerular feedback
• Lungs: Hypoxia causes vasoconstriction (**Unique; other organs: hypoxia → vasodilation)
• Skeletal muscle: Local metabolites - lactate, adenosine, K+
• Skin: sympathetic stimulation most important mechanism; temperature control

• Governed by the starling equation
• P_c = capillary pressure
• P_i - interstitial fluid pressure
• π_c = plasma colloid osmotic pressure (pulls fluid into capillary)
• π_i = interstitial fluid colloid osmotic pressure (pulls fluid out of capillary)
• K_f = filtration constant (capillary permiability)
• 

• Excess fluid outflow into interstitium
• commonly caused by:
• -↑ capillary pressure (heart failure)
• -↓ plasma proteins (nephrotic syndrome, liver failure)
• -↑ capillary permeability (toxins, infections, burns)
• -↑ interstitial fluid colloid osmotic pressure (lymphatic blockage