W1 Flashcards
Where does the excitation of the heart originate?
In the SA node in the pacemaker cells that naturally depolarise by the decreased efflux of potassium ions, transient calcium ion influx and the funny current (sodium and potassium ion influx). Once this depolarisation reaches the threshold then T type calcium channels open and depolarise the cells causing contraction.
How does excitation spread across the heart?
From the SA node—> AV node—> down bundle of his in intraventricular septum—> left and right branches of bundle of his —> up the purkinje fibres. This signal is transferred across the heart by the gap junctions between cells
What changes the heart rate? What is the term for an increase in heart rate?
The autonomic nervous system. Vagus nerve of the parasymapthetic stimulation uses acetyl choline acting on muscarinic M2 receptor.
Positive chronotropic effect
What are the effects of acetylcholine on heart rate, heart force and electrical conduction of the heart?
- decreased HR (negative chronotropic effect) by increasing the difference between the membrane potential and the threshold potential
- decreased contractility (negative inotropic effect) by decreasing calcium influx in phase 2 plateau of atrial and ventricular myocytes AP.
- decreased conduction velocity in AV node (negative dromotropic response) by increasing the delay in AV node due to decreased activity of voltage gated calcium channels (allowing influx)
What are the effects of noradrenaline on HR, heart force and electrical conduction
- Increased HR (positive chronotropic effect) by decreasing the difference between the membrane potential and the threshold potential
- increased contractility (positive inotropic effect) by increasing calcium influx in phase 2 plateau of atrial and ventricular myocytes AP.
- increased conduction velocity in AV node (positive dromotropic response) by decreasing the delay in AV node due to increased activity of voltage gated calcium channels (allowing influx)
Describe the mechanisms which anti-anginal drugs ivabradine reduce HR
Slow down HR by blocking the HCN channels (that allow calcium influx causing depolarisation) this reduces the frequency of the pacemaker cells reaching the AP
State the process of excitation in contraction of cardiac muscle
Four phases-
Phase 4- constant membrane potential from the inward rectifier potassium current (Iki)
Phase0- voltage activated sodium channel activated, sodium moves into the cell (Ina) so depolarisation to reach AP
Phase 1- brief repolarisation due to transient outward current where potassium exits the cell (Ito)
Phase 2- PLATEAU phase (important in force of contraction of heart due to starlings law) Ical channels inward calcium into cell; Iki causing outward potassium
Phase 3- repolarisation back to resting potential from IK
Explain how beta1 adreoceptors activation causes increased contraction force of the heart
Beta-adrenoceptors are coupled to Gs-proteins, which activate adenylyl cyclase to form cAMP from ATP. Increased cAMP activates a cAMP-dependent protein kinase (PK-A) that phosphorylates L-type calcium channels, which causes increased calcium entry into the cells.
What are clinical uses of adrenaline and dobutamine
positive chronotropic (increase HR)
+ inotropic (increased contractility)
+ dromotropic effect ( increased conduction V in AV node)
What are the two hormone system(s) that can increase BP and the single hormone that can decrease BP?
1- renin- angiotensin-aldosterone system
2- ADH
1- natriuretic peptides ANP and BNP
Where are the three hormones in the RAAS system excreted from?
Renin= from kidney
Angiotensin II- lungs
Aldosterone= adrenal cortex
Where is ADH synthesised from ?
What does it cause?
The hypothalamus and stored in the pituitary gland
Increase in MAP due to the reabsorption of water and vasoconstriction of blood vessels to increase svr and BP
What is the mode of action of natriuretic peptides?
Where are they synthesiseD?
The heart
Cause decrease of MAP due to the increased secretion of salt and water hence reducing blood volume and pressure
Explain how smooth muscle contraction occurs
Calcium influx from sarcoplasmic reticulum occurs, this binds to calmodulin to then activate the Myosin light chain kinase (MLCK). This activated complex then activates myosin light chain (MLC).
This allows myosin to bind to actin and muscle contraction to occur
Same process as striated muscle except not with ATP but instead MLC.
Explain how smooth muscle relaxation occurs
Myosin light chain must become dephosphorylated from the MLCK by myosin light chain phosphatase. This returns the myosin back to a resting conformation
How do calcium antagonists treat angina and hypertension
By reducing the amount of calcium ions entering the cell during phase 2 of the AP cycle this reduces the force of contraction of the heart. Hence reducing CO so reduces MAP
Angina- same thing but in the smooth muscle cells so reduces the tone e.g vasodilation so increases perfusion of the heart
What are the two equations of MAP?
MAP = SVR x CO MAP = (2x diastolic + systolic BP)/3 MAP= diastolic BP + 1/3 pulse pressure
What is the rate of flow dependent on ?
What is the equation for rate?
Blood viscosity
Length of blood vessel
Radius of the blood vessel
R= n (viscosity) x L (length of vessel)/ R^4 (radius of vessel)
What murmur is mid diastolic tapping apex
Mary stuck my dick to apple
Mitral stenosis mid-diastolic tapping apex
What is the murmur for pan-systolic murmur raidiating to the axilla?
Mr robinsons picks silly murmurs always
Mitral regurg pan-systolic murmur axilla
What murmur is an early diastolic murmur at the left sternal edge?
Always remember ethan dislikes my left sternal edge
Aortic regurgitation early diastolic murmur left sternal edge
What murmur is an ejection systolic murmur?
Ashton says everything smells magnificent
Aortic stenosis ejection systolic murmur
What drug can be used to increase heart rate by competitively inhibiting the acetylcholine emission
Atropine
What causes the cells for action potentials in the SA and AV to depolarise during phase 4
Due to ICaT opening transiently causing an upstroke of calcium
Ik potassium close
HCN (funny current allowing sodium to enter the cell)
What causes the cells for action potentials in the SA and AV to depolarise during phase 0
IcaL (voltage activated calcium channels allowing influx of calcium ions)
What causes the cells for action potentials in the SA and AV to repolarise during phase 3
Ik (potassium efflux)
What causes the cells for action potentials in the atrial and Ventricular myocytes to depolarise during phase 0
Due to INA voltage activated sodium channels causing sodium influx
What causes the cells for action potentials in the atrial and Ventricular myocytes to temporarily repolarise during phase 1
IKo transient potassium efflux
What is the mode of action of digoxin?
Increases contractility by increasing ventricular function curves
Competitively blocks ATPase pumps in sarcolemma (that contributes to membrane potential) causing build up of sodium in the cell activating the Na+/Ca2+ exchanger to occur so there is then large influx of calcium into the cell, which is used for contraction in the plateau phase to increase contractility
What conditions do beta adrenoceptors antagonists treat?
Block the effects of sympathetic drive by lower heart force, CO, HR and so decrease myocardial o2 requirement
Angina, AF, supraventricular tachycardia
Give some examples of beta blockers that are selective for beta-1?
Atenolol
Bisoprolol
Metoprolol
Give some examples of beta blockers that are non-selective to 2 and 1
Propranolol
Carvedilol
What are some of the side effects of beta blockers?
Bronchospams for non-selectives Bradycardia Hypoglycaemis Fatigue Cold extremeities
Describe some of the features of cardiac muscle
Striated with myocytes gap junctions
Desmosomes giving structural support through intercalated discs
Describe the mechanism of muscles contraction
ATP is hydrolysed on myosin head
Myosin head extends and attaches to actin binding sites (exposed from calcium binding to troponin)
ATP binds to myosin head and so it undergoes a power stroke to the M line
Myosin head relaxes and returns to normal conformation
What is starlings law?
As end diastolic volume increases
Stroke volume increases
What is the normal duration of a PR interval?
O.12s-0.2s
3 small squares to 5 squares
What is the normal duration of the QRS complex?
0.1s
How do you calculate the heart rate from an ECG?
No. Of large squares between two R waves/ 300
OR
Count how many QRS complex in 30 big boxes then times by 10
Define blood pressure
Outward pressure exerted by the blood on the blood vessel wall
In the baroreceptor reflex, what nerve carries the signals to the CNS
Glossopharyngeal nerve
What is korotkoff sound 1?
The first sound of blood flow when taking blood pressure after circulation has been cut off
What is the ECFV and how is it regulated?
Water balance Sodium balance (salt)
Name some humoral agents that will cause vasodilation and so a drop in BP
Histamine
Bradykinin
Nitric oxide (as activates cGMP that signals smooth muscle relaxation)
Describe some local humeral agents that cause vasocontriction
Serotonin
Thromboxane
Leukotrienes
Endothelin
What are some acute responses to exercise
HR and SV increases
Vasomotor nerves reduce flow to kidneys and gut
Metabolic hyperaemia; reducing SVR and DBP
Blood flow to skeletal and cardiac muscles increases
What is starlings law?
As end diastolic volume increases
Stroke volume iwll increase (volume pumped by each ventricle per heart beat)
Hence creating the optimal length for contraction in the cardiac muscle
Define cardiac output
Volume of blood pumped by each ventricle per minute
CO= SV x HR
What side of the stethoscope is used for high frequency sounds and low frequency sounds
High frequency; diaphragm (big)
Low frequency; bell
What is the normal mean arterial blood pressure range? (MAP)
70-105
When doing a 12 lead ecg what are the positions of the chest leads?
V1-V6
V1; right 4th intercostal lateral to sternum
V2; left 4th intercostal lateral to sternum
V3; inbetween v2 and v4
V4; fifth intercostal mid clavicular line
V5; 5th intercostal along from v4
V6; 5th intercostal mid-axillary line
When doing ecg what are the methods to calculate the HR?
Divide 300 by number of large squares between two r waves
Count how many qrs complex in 30 large boxes then x10
