Rest of Cardio

Different types of heart failure

1. Left-sided failure

   • Systolic and Diastolic

2. Right-sided

3. Congestive

Systolic left sided

Reduced LV contractility → reduced ejection fraction

• stroke volume/end diastolic volume

Diastolic left sided

Reduced LV compliance

• reduced diastolic filling → lower end diastolic volume

• same ejection fraction (both SV and EDV decreases)

Right sided

(left-sided causes right-sided)

Increased plasma volume

• right side cannot pump back to pulmonary vein

• blood backs up in the lungs (vena cava side)

• consequence of left sided failure → less blood pumped systemically → backlog in pulmonary circulation

Congestive

Congestion in body tissues due to slow blood flow (hypotension or lack of contractility)

• leads to oedema

Action of Atrial Naturetic Peptide

1. low pressure stretch receptors (volume receptors) in atria walls, detect high pressure

2. ANP and BNP released

3. stimulates glomerular afferent arteriole dilation

4. increased GFR

5. more excretion of Na+ and H20

6. decreased plasma volume (peeing more)

7. vasodilation (stimulation cGMP formation)

8. inhibits RAAS → decreases vasopressin (ADH) and aldosterone production

BNP generated in ventricular myocytes on heart failure

diagnostic marker

Major equations

CO = SV x HR

MAP = CO X TPR (total peripheral resistance)

CO = vol of blood pumped out LV per unit time (proportional to body metabolism

Venous return - blood volume RV per unit tume

ejection fraction = SV/EDV

Preload

• venous return

  • circulating blood volume → impacted by haemorrhage

  • blood distribution btw central and peripheral veins

    • symp NS → peripheral venous tone

    • muscle pumps (gastrocnemius) → propels blood peripherally → centrally

    • thoracic pump

      • negative thoracic pressure and positive abdominal pressire propels blood centrally

degree of cadiomyocyte stretch prior to contraction

Influencers of ventricular filling [5]

• VEDV → ventricular end diastolic volume = preload

1. circulating blood volume

2. venous tone

3. heart rate (reduced HR increases ventricular filling time)

4. myocardial compliance → preload (expansion when filling)

5. venous return → linked to circulating blood volume, blood distribution and venous tone

Heart rate

(Chronotropy)

beats per min (autonomic control)

Contractility (inotropy)

contractile strength at a given muscle length

Afterload

1. total force that opposes sarcomere minus the stretching that existed before contraction

2. pressure that the ventricles must overcome to eject blood (increasing systemic resistance increases afterload)

Pacemaker potential

4 → 0 → 3

phase 4 - funny current If - opening of slow Na+ ions channels

phase 0 - rapid depol → vgated Ca2+

phase 3 - vgK+ channels repolarisation

Ventricular Action Potential

4 → 0 → 1 → 2 → 3 → 4

ventricular - constant resting membrane potential = phase 4

• when receives AP from AV node

  phase 0 - vgated Na+ (fast) - rapid depol

• phase 1 vg Na+ close → ito current

  • slow release K+ current

  • small drop in membrane channel triggers phase 1

• phase 2 - plateau phase

  • Ca2+ influx balances K+ efflux

  • due to opening of vg L-type Ca2+ channels (slow)

• phase 3 - repolarisation

  • Rapid delayed rectifier K+ channels open

  • slow Ca2+ channels close

• phase 4 - resting potential reached again

EDV

Controlled by preload (filling time)

ESV

Controlled by force of blood ejection (contractility)

• Resistance provided via vasoconstriction (MAP) → afterload

Frank Starling

Degree of stretch of muscle fibres dictates the energy for/strength of contractility

• Higher fibre length → greater energy

Not linear

Overstretching impairs contractile function → optimum length for maximum contraction

• Past this point → tension falls

Stroke volume

blood ejected per heart beat

Cardiac muscle ultrastructure

• High mitochondria numbers → High energy dependency

• Gap junctions within intercalated disk → electrically coupled

• Desmosomes within intercalated disc → mechanical disk

Contractility regulation - independent of preload stretch (EDV)

• Greater Ca2+ influx into cytoplasm (cytosol) → lower ESV

  • More blood pumped out → high SV

• Ca2+ induced Ca2+ release

  • DHPR = voltage sensor

  • Ryanodine receptor → SER

• Troponin C → exposure of myosin binding site

  • Troponin → 4 Ca2+ ion binding sites → cross bridges

  • Not usually saturated → higher relative force when more Ca2+ available

  • Power stroke → ATP bound myosin → mechanical force of contraction

    • Positive inotropism

• Voltage gated Ca2+ channels conduct more Ca2+ → faster cardiomyocyte depolarisation

  • Ca2+ promotes faster cell depolarisation (increases conduction velocity)

    • Earlier activation of K+ currents (K+ RAPID delayed rectifier channels) → faster repol → increases heart rate

      • Ca2+ via calmodulin (activates kinase that →) enhances K+ current = faster repol

    • channels open earlier → If → reduced irregular heart beats

    • increased rate of contraction and relaxation

• Sensitisation of troponin to Ca2+ → increase contractility at lower Ca2+ concentrations

• Increased rate of Ca2+ uptake back into SER → faster muscle relaxation

Sympathetic stimulation → positive inotropic effect

• Maximal contractile force increased

• Rate of contraction increased

• Rate of relaxation increased

Intrinsic vs Extrinsic inoptropy

Intrinsic → related to preload

Extrinisic → sympathetic stimulation, movement from one starling curve to another

• contractility independent of stretch

• increasing stroke work regardless of preload and afterload → (higher contractility)

How Ca2+ influences ventricular myocyte contraction

Action potential

• faster plateau phase → 2 (shorter)

• faster repol → 3 (shorter)

Sarcoplasm conc.

• increase influx and efflux → faster contraction

Contraction

• rapid and more powerful contraction → 2

• rapid relaxtion

3 ways altering contractility

1. preload stretch

2. troponin sensitisation

3. change of free Ca2+ conc in cytosol/sarcoplasm

Acetylcholine - weak negative ionotrope

• acts only on atria

• reduces cAMP → less PKA → less Ca2+ release → less contraction

Other factors that decrease contractility

• parasympathetic drive (weak)

• heart failure

• myocardial infarction

• hypoxia

• negative inotropic drugs

  • beta-blockers (less PKA action)

  • calcium channel blockers

  • Na+ blockers → increase Na+/Ca2+ exchange → more Ca2+ pumped out

Increasing cardiac work reduces cardiac efficiency

• little anaerobic capacity

Coronary artery 4-5% of cardiac output

• smaller blood supply relative to other organs

Cause of eccentric hypertrophy

high preload

• thinning chamber

overwork → fibrosis

Cause of concentric hypertrophy

high afterload

• thickening chamber

overwork → fibrosis

worse fibrosis

Chronic stress → fibroblast activation → collagen deposition

• preserved ejection fraction

Increased afterload

• inverse relationship btw afterload and stroke volume

• increased cardiac work

• stroke volume decreases → must increase contractility (positive ionotropic effect)

• high pressure (hypertension) → aortic valve stenosis (narrowing of outflow tract)

mean arterial pressure

MAP = DAP + (SAP-DAP)/3

Pulse pressure

SAP - DAP

SAP - peak pressure → blood ejection

DAP - residual pressure → ventricular filling

Factors influencing peripheral resistance

vessel diameter

vessel length

blood viscolsity

Carotid sinus and Carotid body

Carotid sinus is a dilated area (occipital-internal carotid trunk) at the base of the internal carotid artery, right after the bifurcation of the common carotid artery.

• body = chemical

• sinus = baroreceptors → IN tunical media elastic tissue

  • detects stretch not pressure

  • stretch activates → nerve fibres

    • Tunica adventitia (externa)→ thickened → accomodates afferent nerve endings

Aortic sensors

Aortic bodies and baroreceptor zone

• in aortic arch

Supplied → carotid sinus nerve of glossopharyngeal never (CNIX)

Other sensor locations

• right subclavian artery and R&L pulmonary artery ROOTS

Baroreceptor firing

Signal to raise pressure = increased firing 

• sympathetic outflow

Signal to lower pressure = Gap in firing

• depressor/pressor reflex (parasympathetic outflow dominant)

TPR control

arteriole diameter.radius

• hypertension → increases resistance (higher pressure)

• lower flow

Factors affecting arteriolar radius

Central → neurohumonal (sympathetic, baro, RAAS)

• alpha (constriction) vs beta2 (dilation)

peripheral

• tissue factors

  • metabolites → oxygen = main controlling factor → low = vasodilation

    • functional hyperaemia → increase bloodflow to meet metabolic demand (skeletal muscle)

  • K+ ions (opposite of calcium)

    • low = constriction

    • high = dilation → hyperpolarising current

  • lactate

  • others: pCO2, phosphate, osmality

• vascular factors

  • NO and PG → vasodilators

    • + histamine, bradykinine, ANP

  • constrictors

    • vasopressin

    • (N)Ad

    • 5-hydroxytryptamine

      • seratonon

    • angiotensin II

    • endothelin

    • TxA2 (thromboxin AII)

    • ADP and ATP

• vascular anatomy → number of perfused vessels + mechanical stimuli

Lymph formation

interstial fluid formation → excess drained as lymph

hyrdostatic > colloid (oncotic) pressure

• net movement of fluid out of capillary

arterial end - dominant hydrostatic

venous end - dominant oncotic

sinus rhythm

SA nose acting as pacemaker

(healthy ECG)

Sinus arrhythmia

normal ECG but RR interval varrues

• commonly related to respiration

Sinus tachycardia

normal response to exercise

• hyperthyroidism

• fever

• reflex to low arterial pressure (real or perceived decrease in CO)

Sinus bradycardia

abnormal but indicative of fit intervals

thershold potential

-40MV

Na+ slow influx → funny current

btw -60 → -40MV

when Vg K+ channels open

+30MV

Conduction system → noncontractile cardiomyoctes

• fewer myofibrils

• no intercalataed disks - but sill connected by gap junctions and desmosomes

• more glycogen and mitochondria

Key facts about depol and repol of the heart

SA fastest + dominant

depolarisation: endo→epi (in→out)

repol: out → in (epi→ endocardium)

Moderator band → quick connection to papillary muscle to right ventricle

• Extends from the interventricular septum to the anterior papillary muscle of the right ventricle.

• It’s only in the right ventricle –

• coordinated contraction of both ventricles

  • Moderator band

  • Septomarginal trabecula

  • Trabecula septomarginalis