Ian La Grice Flashcards
What happens to the venous return when the mean right atrial pressure increases?
It decreases due to the increased pressure.
What does equilibrium of the vascular system and heart mean?
It means that the heart and vascular system must work together to increase cardiac output. Blood vessels must increase venus return and heart function must increase togeher, such as when exercising. The autonomic nervous system and the endocrine system connects these two.
What controls the cardiovascular system?
Intrinsic
1) stretch
Extrinsic
1) neural (PNS, SNS)
2) endocrine - Adrenaline, RAS, ADH, NP
What does the adrenal medulla do?
Prduces and stores endogenous catacholamines, including adrenaline and noradrenaline. The adrenal medualla recieves sympathethic innervation, which causes the release of NA and adrenaline into the blood stream.
What is renin releasd in response to?
Sympathetic stimulation via beta 1 receptors.
Decreased pressure in the afferent arterioles
Decreased sodium load in the macula densa
What does angiotensin II do?
a potent vasoconstrictor.
It penetrates the blood brain barrier and activates the hypothalamus pathways which modulate sympathetic outflow to the cardiovascular system and adrenal medulla.
It also stimulates ADH synthesis and induces thirst.
Increases synthesis and release of NA from sympathetic nerve terminals -> to the heart and vessels.
Causes constriction of smooth muscle
Increased release of aldosterone from the adrenal cortex -> reabsorption of Na by the renal tubules.
What is the function of ADH?
Increases water reabsorption
Can also induce vasoconstriction
What are natriuretic peptides?
Synthesised by the heeart, brain and other organs.
Release by the heart is stimulated by atrial and ventricular distension, angiotensin II, endothelin and sympathetic stimulation (beta adrenoceptor mediated) and by neurohormonal stimuli, usually in response to heart failure.
ANP is released in response to hypervoluemic staes and chronic heart failure.
ANP and BNP (brain-type natriuretic peptide)
What are the functions of BNP and ANP?
ATRIAL Naturetic Peptide - atria production
BNP - ventricles
BNP is a sensitive marker for heart failure.
Opposite roles to angiotensin II. - ANG II stimulates this negative feedback.
They cause : Natriuresis Diuresis Increase GFR and filtration fraction Inhibit renin release - decrease circulation angiotensin II and aldosterone Systemic vasodilation Arterial hypotension Reduced venous pressure Reduced pulmonary capillare wedge presure.
This: Decreases blood volume decreases arterial pressure Decreases central venous pressure Decreases pulmonary capillary wedge pressure Decreases cardiac output
Therefore, this system counter regulates RAAS
Neural endopeptidase degrades natriuretic peptides.
What maintains the sinus rhythm?
Suppression of the lower pacemakers
Coordinated excitation via specialised conduction system
Existence of a prolonged refractory period in the myocardium
There are two periods during an action potential when it is difficult to create a new action potential. What are those called
Relative refractory period
Supernormal period
Need a larger or smaller stimulus than normal but they generate a slow conduction action potential.
What is an arrhythmia?
1) Disorder of impulse formation - early discharge of a pacemarker by an unstable resting membrane potential in working myocardial cells. tachycardia and bradycardia
2) Disorders of impulse conduction - Conduction abnormalities such as partial or complete AV block, left or right bundle branch block and reentry. The first gives rise to a slow heart rate or bradycardia, while the others alter the time course of the ventricular spatial or temporal dispersion of repolarization.
What are the types of reentrant arrhythmias?
Atrial flutter - fast regular ,atrial rate (250-350 bpm). Organised (same) action potentials. Heart block may develop
Atrial fibrillation - Raid disorgansied atrial activation (350-600 bpm). Not all impulses conducted to ventricles. Rapid disorganized ventricular rhythm. Risk of embolisation. due to blood stasis.
Ventricular tachycardia: rapid ventricular activation (110-250 bpm) Impaired mechanical function and risk of ventricular fibrillation..(wide QRS)
Ventricular fibrilation - chaotic ventricular rhythm leads to circulatory arrest and death.
What cases the prolonged refractory period in cardiac cells?
The dependence on the Na channels for the membrane potential to decrease before they can be refired.
What does increased vulnerability to recurrent activation increase with?
Decreased conduction velocity
Decreased refractory period - a smaller refractory period means that the cells can reset and be stimulated earlier (in time for the conduction to induce activation)
What do you need for re-entrant activation?
A circuit Slow conduction or short effective refractory period Unidirectional block (so conduction doesn't go both way A trigger (something to set the conduction off).
Reentrant circuits can be functional or anatomical.
What is a potential complication with wolf-parkinson white syndrome?
If atrial flutter or fibrilation develops then there is nothing preventing the action potential from going straight into the ventricles.
What determines the rate of propagation of electrical activation?
Electrical properties of the myocytes -increased electrical coupling between myocytes increases propagation rate. Propagation is greatest in large diameter cells.
Inward current during excitation - density and status of Na channels is important - greater current faster propagation.
Ca channesl are slow at influx and that is why the SA and AV nodes are slow conduction.
What does myocardial ischaemia result in?
A potential for an arrhythmia. This is what causes death.
Myocardial ischaemia causes
1) slow conduction
2) reduced AP duration
3) non-uniform repolarization
4) ectopic activation
Need a reduced wavelength caused by reduced conduction rate and reduced refractory period. Then a trigger.
Slow conduction:
a) ischaemic tissue is low in ATP
b) Na/K ATPase reduced
c) transmembrane Na, K gradients reduced
d) partial membrane depolarization
e) inactivation of Na channels
f) reduced gap junctions coupling (low pH due to regional metabolic acidosis).
Reduced action potential duration
a) Na/K ATPase reduced
b) transmembrane Na, K
c) inactivation of Na channels
d) hyperkalaemia outside of the cell -> activates a potassium channel that repolarises the cell
Ectopic activation -delayed after depolarisation - impaired Ca homeostasis in myocardial ischaemia leads to elevated intracellular Ca2+ from SR.-> spontaneous release. Na/Ca exchanger then tries to remove 1Ca bringing in more 3Na -> depolarising current -> start of arrhythma.
Non-uniform repolarization - conduction block
If ventricle tachycardia develops this causes an increased energy demand that further increases the ischaemia and leads to ventricular fibrilation
What is an issue for someone with a past MI?
Monomorphic VT generated from the damaged tissue.
How does heart failure generate arrhythmia?
Heart failure is associated with an increased risk of VT and VF becauee it is associated with remodelling, fibrosis, scaring, altered ANS and cellular electrical properties.
a) Atria are dilated -> increased duration of circuit -> reentrant circuit can develop.
b) Increased atrial pressure stimulates stretch receptors
c) Heart failure causes atrial fibrosis - slowing of conduction
d) Altered expression of Na/Ca exchanger
e) ANS inputs change
f) AF promotes more AF
g) HF has increased risk of VT and VF
What is an early after depolarization and what is the risk?
Early after depolarizations are caused by prolonged action potentials which enable the calcium channels to re-activate. This promotes the T wave.
Long QT syndrome prolongs the action potential duration. This prolongs the vulnerable period for arrhythmia and can cause an early after depolarisation.
Increased action potentials are caused by:
a) drugs - amiodarone (is supposed to prolong the action potentials to prevent reentrant circuits)
b) Reduced extracellular potassium concentration - decreases channel function
c) potassium ion channel mutation leading to reduced effectiveness of the delayed rectifier
d) Na ion channel mutations that affect inactivation of the channel.
They can result in continuously varying polymorphic VT (torsade de pointes. May resolve spontaneously or progress to VF.
What order to you check a ECG?
Rate, rhythm, P wave, PR interval, QRS, QRS axis, Q wave, ST segment, T wave, QT interval.
What are the possible causes of polymorphic ventricular tachycardia?
Long QT syndrome -
Signs:
family history, presyncope, and ECG showing QT interval and VT morphology
Why is VT caused by long QT polymorphic?
Because it is not anchored by structural abnormalities. Activation drifts around the heart.
What advice do you give someone with long QT syndrome?
Avoid lifestyle modifications and medications that prolong QT.
LQT1 - stress, exercise
LQT2 - auditory stimuli, stress
LQT3 - rest and sleep
Beta blockers and ICD
How do you treat someone with long QT syndrome?
Lifestyle modifications.
Beta blockers and implantable cardioventer defribulator placement
Why is their a low blood pressure with VT?
VT leads to reduced ventricular filling
VT leads to impaired pump function
Poor coordination of ventricle
These cause reduced CO and therefore, the mean artrial pressure is low. This leads to poor brain perfusion.
What do you do for monomorphic ventricular tachycardia?
Defibrillator
Antiarrhythmia medication
Ablation of reentrant circuits
What affects the inotropic state?
The magnitude and rate of Ca released from SR
Amount of Ca in the SR
Affinity of troponin C for Ca
How does sympathetic activation affect inotropy?
It causes activation of adenylate cyclase through stimulation of the adenylate cyclase with NA. This increases cAMP which activates PKA which phosphorylates the Ca channels and keeps them open. It also phosphorylates the L-typr Ca channel receptors, the ryanodine receptors, troponin I and other proteins. This leads to increased faster Ca kinetics, increased opening of the L-type channels and stimulation of SR and cell membrane Ca pumps.
Stimulation of the M2 receptors does the opposite and increases K+ leaving the cell.
Why does cardiac muscle have a steeper force length relationship than skeletal muscle and why is there no descending limb?
Because when the muscle stretches, troponin C has an increased sensitivity for Ca. There is no descending part because cardiac muscle can not be stretched so that the myosin and actin is not overlapping.
What is the main way that heart beat increases?
The PNS shuts off. At rest the PNS keeps the HR low and when this shuts of the heart rate increases.
Why does an ectopic beat increase the chance of reentry?
If the ectopic beat occurs during the refractory period then the Na channels are not fully reset so there is reduced Na current (slow propagation)
Because some cells will be reset and others not their is a greater chance of a conduction block (unidirectional).
What is a secondary issue if you have cardiac ischaemia driving VT?
the VT increases th energy demand of the heart. This increase the O2 demand, but with reduced supply. This increases the ischaemia and can lead to fibrillation.
What type of VT develops in a healed MI?
Monomorphic
What is the mechanism for torsade de pointes being caused in long QT?
Long QT syndrome causes prolongation of the APD -> increased risk of developing an EAD by the refiring of Ca channels -> this also causes a dispersion of refractoryness resulting in Torsade de pointes
What type of drugs increase the QT interval?
Anti-arrhythmia Anti-depressive Anti-histamine Ant-biotics anti-psychotics
What is one way to treat a monomorphic ventricular tachycardia?
Ablating the reentrant circuit
What happens to cardiac cells in hypoxia?
Reduced ATP: Reduced Na/K pump - this reduces the Na and K concentration gradients - causes hyperkalaemia - reduced resting membrane potential - reduced action potential duration -Reduced Na/Ca exchange
Reduced sarcolemmal Ca2+ extrusion
- increased cytoplasmic Ca
- impaired relaxation
- electrical instibility
Recuced pH
- H competes with Ca on troponin C
- reduced ionotropic state
Reduced nexus junction coupling (slow conduction)
How does the heart contract by so much considering the muscle cells can only contract 12%?
Because myocardial sheets shear along each other resulting in an increase in the angle of those sheets causing the wall to thicken.
The septum and anterior left ventricle wall also shears in opposite directions
Circumferential shortening, longitudinal shortening, torsion, transmural sear all causing radial wall thickening.
Changing orientations of the myocytes in the lamina structure
What does sympathetic activity do to action potential duration?
Shorten it.
What is the effect of sympathetic nerve activity on the heart?
Increase rate - slow (lots of second messengers and nothing to break down NA)
Duration is reduced
Contraction is increased
The systolic contraction needs to occur quicker so that there is more time to fill the ventricles during diastole. This combined with faster filling.
What is the difference between stimulation of the left and right stellate ganglia (sympathetic NS)?
Left - contractility of the left ventricle
Right - increased heart rate and mild increase in contractility
What happens to the heart with PNS stimulation?
Reduced HR - rapid because of direct coupling to the K+ channel (acetylcholine is also mopped up quickly by acetylcholine esterase) to turn of PNS stimulation)
Action potential duration is reduced (similar to with sympathetic stimulation)
Decreased ionotropic state of the atria (less ventricle innervation)
What determine the oxygen demand of the heart?
Basal metabolism
Wall force development - depends on after load (pressure and geometry of the heart [dilated heart requires increased force for the same pressure generated])
Ionotropic state - increases ATP requirements
Heart rate
What determines the oxygen supply to the heart?
Draw graph
- aortic pressure and extravascular compression
determine the perfusion pressure
Impedence (determined by local regulation of vessels).
Q = Change in P/R
MV02 = Q(CaO2 - CvO2)
To increase -
Increase oxygen concentration
Increase extraction
Increase flow
When does blood flow in the coronary arteries?
Contraction of the heart muscles impedes the capillaries in the heart. Therefore, blood flow is low in the coronary arteries during systole . Much higher is diastole. This is a problem when HR increases because diastole decreases.
This is much more significant in the left ventricle because of the higher pressures.
Local control of the coronary arteries is via the metabolic hypothesis -> increased work -> vasodilation
What is the diastolic pressure time index?
It is the subendocardial blood flow/ oxygen supply. This is highest during systole and can be demonstrated on a pressure time graph.
DPTI = coronary perfusion pressure x diastolic time
CPP = diastolic aortic pressure - LV EDP
What is the tension time index?
TTI = systolic pressure x systolic time
It is the oxygen demand caused by contraction of the ventricle.
What is the function of acetylcholine on the vascular endothelium?
Binds to the M3 receptor on endothelial cells - stimulation of NO synthetase -> NO production -> leading to smooth muscle relaxation
What is the function of acetylcholine in vessels with damage?
It acts on M2 and M3 receptors directly on the VSM activation Gq and Gi pathways leading to increased Ca2+ -> contraction
How does amilodipine help someone with angina and coronary artery spasm?
It increases coronary artery dilation (reduces spasm) -> increasing O2 delivery
- Reduction of oxygen utilisation - reduces arterial pressure at rest by dilating arteriles and reducing the TPR (after load and preload).
- this reduces the hearts demand for oxygen.
What happens to TPR and CO in anaemia?
TPR decreases due to the metabolite hypothesis and the CO increases because of sympathetic stimulation.
What causes a high pulse pressure?
Increased runoff and lower diastolic pressure - peripheral dilation causes this.
How much can you increases the blood flow through the coronary artery and what is this called?
5 x and coronary reserve capacity
What are the two types of heart failure?
Heart failure with preserved ejection fraction (diastolic) >50% - not dilated (yet)
Heart failure with reduced ejection fraction (systolic) - <40-50% - dilation
What are the features of HF with preserved ejection fraction>
> 50% ejection fraction - heart not dilated (yet)
Symptoms usually with exercise rather than at rest.
no effective treatment.
Occurs in older, female, hypertensive, diabetic, AF, chronic kidney disease
Normal systemic function but poor LV function
What are the differences between systoluc and diastolic HF?
Ejection fraction:
Systolic -decreased
Diastolic - increased
Left ventricular mass:
Both increased
Relative wall thickness:
Systolic - decreased
Diastolic - increased
EDV:
Systolic - increased
Diastolic - normal
End diastolic pressure:
Systolic: increased
Diastolic: increased
Left atrial size:
Both increased
What happens to the muscles cells during diastole?
X-bridge detachment
Ca2+ removal
Elastic recoil
They need to be compliant (titin and collagen)
How do you calculate MAP?
MAP =DP + 1/3(SP - DP)
How do you tell in a bundle branch block if the block is in the left or right side?
The coduction will go from the normally conducted side and then spread to the other side. If the block is in the left, then the conduction will go from left to right. Thus, the conduction axis will be normal. If from right to left then lead 1 and 2 will be negative.
How do you tell in a bundle branch block if the block is in the left or right side?
The conduction will go from the normally conducted side and then spread to the other side. If the block is in the left, then the conduction will go from left to right. Thus, the conduction axis will be normal. If from right to left then lead 1 and 2 will be negative.
What is the consequence of LBBB on ventricular filling and ejection and on muscle contraction?
The ejection is prolonged resulting in a reduced filling phase.
Long valve motion.
Slow conduction causes non-synchronous contraction resulting in some parts contracting and others increasing in length. This compresses blood vessel at different time. Can result in hypoperfusion of some areas.
What is cardiac resynchronization?
Using leads to make the ventricles at the same time.
One lead in the atrium and one in each ventricles
To get to the left ventricle go through the coronary sinus to the epicardial surface of the left ventricle.
No extra energy demand.
What is cor pulmonale?
RHF caused by high blood pressure caused by chronic lung disease.
What are the causes of pulmonary hypertension causing cor pulmonale?
Loss of capillary beds (COPD)
Vasoconstriction caused by hypoxia, hypercapnia.
Increased alveolar pressure (COPD)
What would you see on an ECG of RHF?
Right sided axis deviation
Increased amplitude of the qrs.
What specifically causes mitral stenosis?
Fibrosis that causes thickening of the leaflets, o with calcium deposits
Which chamber gets larger in mitral stenosis?
Left atrium
What causes the increased first heart sound in mitral stenosis?
The stiffness of the valves causes them to snap shut. They should be partially closed when the ventricles begin contracting but in MS they are wide open so snap shut for a greater distance.
Why can you develop arrhythmias in mitral stenosis?
Structural remodeling of the left atrium.
LA distension and hypertrophy and fibrosis.
The LA enlargement increases the path length.
Inflammation and fibrosis further contribute to a tortuous conduction and activation delays that facilitate unstable electrical activity.
Varying ANS remodeling changing the excitability in different regions
What is the progression of atrial fibrillation?
One event
Persistent events
Then becomes persistent events
What are the possible treatments for AF?
Rhythm control: Amiodarone Sotalol (beta blocker) Ablation therapy Dc conversion
AF rate control:
Ca channel blocker
Beta blocker
Digoxin
Can’t forget warfarin
How does aortic stenosis develop?
In old age the calcification occurs. It begins with endothelial damage from increased mechanical stress. Inflammation occurs then deposition of LDL cholesterol. The valve becomes thickened.
In younger people it is often caused by a bicuspid valve.
What can aortic stenosis cause in the heart?
HFpEF. The LV has to generate a higher pressure to eject through the valvle leading to problems with relaxation. This cna progress to HFrEF
The calcification can also cause LBBB.
