CVS Flashcards
Diffusion resistance is dependent on 3 things, what are they?
Nature of the molecule, nature of the barrier, path length
What will the concentration gradient between a capillary and tissue be dependent on?
The rate of substance use by the tissue
The rate of blood flow to the tissue through the capillary bed
Normal cardiac output for a 70kg man at rest is:
5l.min-1
State 2 tissues that need a constant level of blood flow.
Brain and kidneys
What 3 things influence the exchange of substances between the capillaries and surrounding tissues?
Surface area (capillary density), diffusion resistance & concentration gradient
What blood flow does the brain receive at rest and during exercise?
750ml.min-1 (0.75L.min-1) at both rest and exercise
What is the blood flow of the heart at rest and during exercise?
300ml.min-1 (0.3L.min-1) at rest.
Increases to 1200ml.min-1 (1.2L.min-1) during exercise.
What is the normal blood flow to the gut? When does this increase, and by how much?
Normally, 1400ml.min-1 (1.4L.min-1).
This increases following a large meal for absorption of nutrients.
Increases up to 2400ml.in-1 (2.4L.min-1)
Which tissue can increase its blood flow by the most?
Give values.
Skeletal muscle - by 16 times.
At rest only 1L.min-1. Increases up to 16L.min-1 during exercise.
Define resistance in terms of blood vessels.
Reducing the ease with which some vessels are perfused in order to re-direct blood to areas that are more difficult to perfuse. (E.g. To the brain against gravity)
Define capacitance in terms of vessels.
The ability of the veins to provide a temporary and variable store of blood so that the rate of blood return to the heart and total flow in the system can be varied.
Describe the distribution of blood volume in the circulation at any point in time.
67% of blood is in the capacitance vessels (veins).
17% within the heart and lungs.
11% within the arteries and arterioles.
5% within the capillaries.
In which area of the mediastinum is the heart situated?
Inferior, middle mediastinum
What landmark separates the inferior mediastinum from the superior?
Sternal angle (angle of Louis / manibriosternal joint)
As well as the heart, what else is found in the middle mediastinum?
Great vessels (aorta, pulmonary trunk, superior vena cava, pulmonary veins), nerve (e.g. Phrenic), trachea bifurcation and lymph nodes.
What is found anterior (anterior mediastinum) and posterior (posterior mediastinum) to the heart?
Anterior - very little - some fatty tissue and thymus gland in children.
Posterior - oesophagus, aorta and thoracic duct
Which ribs does the heart lie between?
Ribs 1 to 6
What is found at the 4 borders of the heart?
Superior border = superior vena cava, aorta and pulmonary arteries.
Left border = mostly left ventricle. Some pulmonary artery and the auricle of the left atrium.
Inferior border = right ventricle.
Right border = right atrium
What is the function of the pericardium?
Limits the hearts motion in the mediastinum, prevents excessive dilation on volume overload, lubricates to prevent friction during pumping & protects the heart from infections spreading from surrounding organs.
What are the 4 layers of pericardium From superficial to deep?
- Fibrous Pericardium
- Parietal serous pericardium
- Pericardial cavity
- Visceral layer of serous pericardium
Phrenic nerve is derived from spinal nerves…
C3, C4, C5
Do the phrenic nerves pass anteriorly or posteriorly to the lungs?
What about the lung roots?
Which phrenic nerve passes more posteriorly than the other?
They both pass posteriorly to the lungs.
Both pass anteriorly to the roots of the lungs
Right phrenic nerve passes more posteriorly (across the right atrium) compared to the left (left ventricle).
Within the heart and related structures, what does the phrenic nerve supply?
The fibrous pericardium and the parietal layer of the visceral pericardium.
What is pericarditis?
inflammation of the pericardium
Give 3 causes of pericarditis.
Infection, inflammatory conditions (e.g. RA or SLE) or metabolic conditions (e.g. Renal failure, hypothyroidism)
What is the main problem associated with pericarditis?
Thickening of the fibrous pericardium can cause constriction of the heart and limit filling during diastole.
What is pericardial effusion?
An abnormal amount of fluid between the heart and pericardium (in the pericardial space).
Give 3 causes of pericardial effusion.
- Pericarditis
- Infection
- Trauma (e.g. Stabbing) - post-operative
What is the main complication of pericardial effusion?
Cardiac tamponade - fluid constricts the heart leading to reduced ventricular filling during diastole and therefore haemodynamic compromise.
How many pulmonary arteries normally enter the heart?
4
Where is the transverse pericardial sinus found?
Behind the pulmonary trunk and ascending aorta when the heart is in situ
Where is the oblique pericardial sinus found?
On the posterior surface of the heart - primarily behind left atrium
Where do the 2 coronary arteries branch from the aorta?
At the left and right aortic sinuses - buldges just above the aortic valve at the origin of the ascending aorta
Name the 2 branches of the left coronary artery, and approximately where they are located.
- Left circumflex artery - around the left superior heart to the posterior surface with the marginal branch branching off to supply the left border.
- Left anterior descending artery - down the anterior surface of the heart (approximately between the two ventricles)
Name the 3 branches of the right coronary artery and where they are approximately located.
- Posterior descending artery - down the posterior surface of the heart.
- Right marginal artery - along the inferior border of the anterior heart.
- Sinuatrial nodal branch - around the top of the heart to the posterior surface and to right atrium.
Name the 3 major branches of the cardiac veins.
What do they drain into?
Small cardiac vein - inferior, anterior surface (RHS).
Middle cardiac vein - posterior surface (LHS).
Great cardiac vein - anterior surface and wrap around inferior surface (LHS).
Draining into the coronary sinus.
What are the 3 unpaired arteries branching off the abdominal aorta?
- Celiac trunk
- Superior mesenteric artery
- Inferior mesenteric artery
Which arteries are major elastic arteries?
Large arteries - aorta, pulmonary arteries, brachiocephalic, left common carotid, left subclavian and common iliac arteries.
What is meant by elastic conducting arteries being ‘pressure reservoirs’ or ‘auxiliary pumps’?
Walls of the arteries stretch during systole as left ventricle contracts.
Walls record during diastole to maintain blood pressure.
Under the microscope, how are muscular distributing arteries clearly defined?
Well developed internal elastic lamina.
What is an ‘end artery’?
A terminal artery supplying all or most of the blood to a body part without collateral circulation.
Name 3 end arteries.
Coronary, splenic and renal arteries
Name 2 absolute end arteries.
Central artery to retina, labyrinthine artery to the internal ear.
What are meta-arterioles?
Those arterioles that supply blood to the capillaries.
What is the process of ‘bridging’ in reference to the coronary circulation?
Muscle grows around one of the larger coronary arteries. The artery becomes compressed during systole
How wide is a normal capillary?
7-10um in diameter.
What are the 3 types of capillary?
Continuous, fenestrated and discontinuous
Post-capillary venules are more permeable than capillaries, true or false?
True
What size are post-capillary venules?
10-30um
Where do leukocytes primarily migrate out of the blood from?
The post-capillary venules
What are venae comitantes?
Give 2 examples.
Deep veins that in certain anatomical positions accompany one of the smaller arteries on either side.
The artery promotes venous return and also warms the venous blood returning to the heart.
Ulnar venae comitantes and tibial venae comitantes.
Which type of artery has a discontinuous internal elastic lamina?
Elastic arteries
What would you find in the tunica media of elastic arteries?
40 to 70 layers of fenestrated elastic membranes (stained black), smooth muscle cells (red), collagen (blue).
Thin external elastic lamina.
What are vasa vasorum? Where would you find these?
Vessels supplying vessels - in the tunica adventitia of large arteries.
What would you find in the tunica media of muscular arteries?
40 layers of circularly arranged smooth muscle cells. Connected by gap junctions.
Prominent external elastic laminar.
What is the diameter of arterioles?
How many layers of smooth muscle might you find in the tunica media of arterioles?
1 to 3 layers. Sometimes a single SM cell in small arterioles.
Which vessel type has no external elastic lamina and very little tunica adventitia?
Arterioles.
Which vessel type has pre-capillary sphincters?
Meta-arterioles
Describe the structure and function of pre-capillary sphincters.
A single smooth muscle cell encircling the endothelium or a capillary. Controls flow into the capillary bed.
What is the structure of continuous capillaries?
Where are they found?
A continuous endothelial layer with cell joined by tight junctions.
Muscle, nervous and connective tissue.
Describe the structure of fenestrated capillaries.
Where are they found?
Pored exit across the endothelium.
Found in the gut, endocrine glands and renal glomerulus.
Describe the structure of discontinuous capillaries.
Where are they found?
Large gaps exist in the walls with an incomplete basement membrane. Allowing the movement of whole cells between blood and tissue.
Found in the liver, spleen and bone marrow.
Describe the structure of a venous valve.
When do they appear?
Extensions of the tunica intima into the lumen.
Appear in larger venules (>1mm).
What is the diameter of large veins?
> 1cm
Describe the structure of veins.
Thicker tunica intima which merges with tunica media.
Tunica media is thin with only a few layers of smooth muscle (except in superficial veins of the leg).
Well developed tunica adventitia with vasa vasorum.
What is the total cross section of the aorta?
2.5cm^2
What is the total cross sectional area of the capillaries?
4500cm^2
Which cells produce the elastin, collagen and ECM of the tunica media?
Smooth muscle cells
Describe aortic dissection.
Blood breaks through the tunica intima of the aorta. It enters the regions between the elastic Lamellae of the tunica media so that layers of the tunica media begin to separate and weaken the aortic wall.
The lymphatic vessels junction with the venous vessels where?
Internal jugular and subclavian veins
Name 3 tissues that are not supplied by blood vessels.
Cartilage, cornea and epithelium
Define ‘stroke volume’
The volume of blood ejected from the heart with each cycle. Or EDV - ESV.
Stroke volume is usually about…
70ml
The equation for cardiac output is:
HR X SV (70 X 70) = 4.9L/min
What prevents inversion of atrioventricular valves?
They are attached to the papillary muscles of the ventricles via chordae tendinae. These muscles contract during systole pulled the chordae tendinae taught and preventing inversion of atrioventricular valves and back flow of blood.
How long is electrical activity delayed at the AV node approximately?
120ms
How many of the cardiac cycle steps are systole and how many are diastole?
3 systole, 4 diastole
What are the 7 stages of the cardiac cycle starting with atrial contraction?
- Atrial contraction.
- Isovolumetric contraction.
- Rapid ejection.
- Reduced ejection.
- Isovolumetric relaxation.
- Rapid filling.
- Reduced filling.
How much of ventricular filling does atrial contraction account for?
10-20% only
At what stage in the cardiac cycle is EDV reached?
At the end of atrial contraction
What is a normal EDV value?
120ml
At what stage in the cardiac cycle does the mitral valve close?
At the end of atrial contraction / beginning of isovolumetric contraction of the ventricles.
What is isovolumetric contraction?
Contraction of the ventricular walls but will all valves closed so there is no change in the volume of blood contained within them. Causes a huge increase in intraventricular pressure.
At what stage of the cardiac cycle does the aortic valve open?
Beginning of rapid ejection / end of isovolumetric contraction.
What is happening to the atria while there is reduced ejection from the ventricles?
They are increasing in pressure as blood flows passively into them.
What causes the aortic valve to close?
A very brief back flow of blood as the ventricle becomes lower in pressure than the aorta at the beginning on isovolumetric contraction (end of reduced ejection).
What is the dicrotic notch?
A very brief increase in aortic pressure as the aortic valve closes.
When is ESV reached?
At the end of reduced ejection / beginning of isovolumetric relaxation.
What is meant by isoelectric relaxation?
Relaxation of they ventricular walls but since all valves are closed, there is no change in blood volume inside the ventricles. This leads to a huge decline in ventricular pressure.
When does the mitral valve open?
When the pressure in the ventricles falls below that of the atria at the end of isovolumetric relaxation.
Is rapid filling a passive or active process?
Passive - no contraction involved.
What is another word for the cardiac cycle stage of reduced filling?
How full are the ventricles at the end of this stage?
Diastasis.
Should be 80-90% full
Which stages of the cardiac cycle does systole comprise of?
Isovolumetric contraction.
Rapid ejection.
Reduced ejection.
How long is the entire cardiac cycle on average?
0.9s
How long does systole last?
What proportion of the cardiac cycle is this?
- 35s
0. 35 / 0.9 = 0.38 = about 1/3
How long does diastole averagely last?
What proportion of the cardiac cycle is this?
- 55s
0. 55 / 0.9 = 0.61 = 2/3
What are the changes in jugular venous pressure a reflection of?
The changes in atrial pressure during the cardiac cycle.
What do the following parts of the jugular venous pressure graph correspond to: A wave, C wave, X descent, V wave, Y descent.
A wave = atrial contraction C wave = tricuspid valve closure. X descent = pulling of atrial base downwards during ventricular contraction. V wave = atrial filling Y descent = rapid ventricular filling
Where do you listen for the aortic valve?
2nd intercostal space, right sternal border
Where do you listen for the pulmonary valve?
2nd intercostal space, left sternal border.
Where do you listen for the tricuspid valve?
4th intercostal space, left sternal border.
Where do you listen for the mitral valve?
5th intercostal space of the mid-clavicular line (at the apex).
What is Erb’s point?
Where is it?
The point where S2 is best auscultated.
3rd intercostal space on left sternal border.
What is the ‘lub’ heart sound?
S1 = atrioventricular valves closing
What is the ‘Dub’ heart sound?
S2 = semi-lunar valves closing
When might S3 heart sound be heard? Is this normal?
Early diastole due to deceleration of blood from left atrium to ventricle.
Normal in children, pathological in adults (congestive heart failure).
When might S4 be heard? What causes it?
Late diastole during atrial contraction.
Associated with stiff, low compliant ventricles.
What are the 5 broad categories that murmurs can be divided into?
- Ejection systolic.
- Pan systolic.
- Early diastolic.
- Mid-diastolic.
- Systolic & diastolic = continuous.
What type of murmur (when does it occur) would aortic valve stenosis cause?
Ejection systolic - occurring at the beginning of systole.
Between S1 and S2.
When is an atrial septal defect murmur heard?
Ejection systolic - when atria are filling during early systole.
What 2 causes of murmur are pansystolic?
Mitral regurgitation (or tricuspid). Ventricular septal defect.
What is the main cause of an early diastolic murmur?
Semi-lunar valve regurgitation (aortic or pulmonary valves).
When would atrioventricular valve (mitral and tricuspid) stenosis be heard?
Mid-diastolic - when atria contract
Give 2 causes of a murmur that is heard throughout both diastole and systole.
Pericarditis and patent ductus arteriosus
Why can S2 sometimes be heard physiologically as split?
During inspiration it can be split as the lower intrathoracic pressure aids venous return and results in pulmonary valve closing slightly after the aortic.
On a radiograph, when can cardiomegaly be diagnosed?
When the cardio thoracic ratio is >50%. (Heart takes up more than 50% of thorax).
Name 5 features of the right atrium.
Superior and inferior vena cava opening. Fossa ovalis. Atrioventricular orifice. Sinus vanarum. Orifice of the coronary sinus.
What is the name for the muscular ridges found in the ventricles?
Trabeculae carneae
What is the conus arteriosus / infundibulum?
The anterior superior part of the right ventricle that forms the entrance to the pulmonary trunk and is conical in shape.
Which cardiac veins drain directly into the right atrium, rather than the coronary sinus?
The anterior cardiac veins on the anterior, right heart
What is the crista terminalis?
The boundary between the rough and smoothed walled parts of the right atrium. Divides the 2 different embryological origins of the atrium (primitive atrium and sinus venosus).
Where are the pectinate muscles found?
On the surface of the rough walled part of the atrium.
How many papillary muscles are in the left and right ventricles?
3 in the right, 2 in the left
What is the moderator band?
A band of tissue in the right ventricle running from the inter ventricular septum to the papillary muscles. Carries part of the right bundle branch of the conduction system to allow co-ordinated contraction of papillary muscles.
What is the aortic vestibule?
Smooth walled, Outflow region of the left ventricle derived from the bulbus cordis.
Which heart valve is the odd one out? Why?
Mitral valve - only has 2 cusps rather than 3.
What embryological tissue does the cardiogenic field form from?
Splanchonopleuric mesoderm
What brings the two endocardial tubes of the cardiogenic region together at the midline?
Lateral folding of the embryo
What initially brings the fused endocardial tube into the thoracic region?
Cephalocaudal folding of the embryo
What are the 6 regions of the developing heart tube In order from top to bottom?
Aortic roots, truncus arteriosus, bulbus cordis, primitive ventricle, primitive atrium, sinus venosus.
What causes the heart tube to fold?
Growth into a fixed space - fixed by the pericardial sac. And differential growth of the different regions.
During looping of the heart tube, in what direction does the cephalic / cranial end fold?
Inferiorly / caudally, anteriorly / ventrally & to the right (VCR)
During looping of the heart tube, in what direction does the caudal end fold?
Superiorly, posteriorly / dorsally and to the left
What does the left sinus horn of the sinus venosus form?
The coronary sinus
Describe the formation of the vena cavae from the sinus venosus.
Sinus venosus divided into right and left sinus horns. Venous system remodels so that all systemic blood drains into right sinus horn via the superior and inferior vena cava. Left sinus horn ceases to grow. The right sinus horn is absorbed by the enlarged right atrium.
Describe the formation of the pulmonary veins and left atrium.
Primitive atrium sprouts a pulmonary vein which bifurcates and bifurcates again forming 4 branches. As the left atrium grows it absorbs the first 2 sets of branches into its posterior wall. Means that most of the LA wall comes from the pulmonary veins and only a small part from the primitive atrium which is displaced left.
The ductus venosus does what?
Shunts blood from the umbilical vein into the IVC past the liver.
What type of blood (oxygenated or deoxygenated) does the superior vena cava contain during embryology?
Deoxygenated.
What is the role of the ductus arteriosus?
Shunts deoxygenated blood from the pulmonary trunk to the aorta from high to low pressure in order to bypass the non-functioning lungs.
What causes closure of the ductus arteriosus at birth?
Increased oxygen saturation of blood causes muscular contraction in ductus arteriosus walls.
Later undergoes fibrosis to anatomically close.
Where is the ligamentum venosum found? What is it a remnant of?
On the posterior liver. A remnant of the ductus venosus.
What is the remnant of the umbilical vein?
Ligamentum teres
How many aortic arches are there?
5 - 1, 2, 3, 4 & 6
What do the two 4th aortic arches form on the left and right hand sides?
Right - proximal right subclavian artery.
Left - arch of the aorta
What do the two 6th aortic arches form on the left and right hand sides?
Right - right pulmonary artery
Left - left pulmonary artery and ductus arteriosus
Where is the recurrent laryngeal nerve found on the left and right hand sides?
Right - hooked around right subclavian artery level T1-T2.
Left - hooked around ductus arteriosus level T4-T5.
Put the following into order: ostium secundum, foramen ovale, septum primum, ostium primum, septum secundum.
Septum primum, ostium primum, ostium secundum, septum secundum, foramen ovale.
What is the primary interventricular foramen?
The small gap left by the muscular portion of the interventricular septum between itself and the endocardial cushions. Will be filled in by the membraneous portion.
What is the conotruncal septum?
The septum that separates the outflow tract into aorta and pulmonary trunk.
Why are the aorta and pulmonary trunk twisted around one another?
The bulbar ridges that form on opposite wall in the inferior truncus arteriosus grow towards the midline separating the outflow tract into left and right sides. This septation proceeds superiorly and inferiorly and as it does so, it twists.
What 3 things does the bulbus cordis form?
Trabeculared RV (proximal 1/3). Outflow tract (conus cordis portion). Roots and proximal aorta & pulmonary trunk (truncus arteriosus portion).
What is the normal oxygen saturation of arteries?
Close to 100%
What is the normal oxygen saturation of the veins?
About 67%
What are the 3 main causes of congenital heart defects?
Genetic, environmental (e.g. Teratogenicity) or maternal infection
What is the main risk of a left to right shunt?
Increased pulmonary arterial and venous pressure
In what 4 places can a left to right shunt occur?
Atrial, ventricular, atrioventricular (abnormal formation of ECs) or aorto-pulmonary / ductal.
Why are left to right shunts acyanotic?
There is no deoxygenated blood entering the systemic circulation so that the oxygen saturation of the systemic circulation remains the same. Oxygenated blood entering the deoxygenated circulation.
Give 3 possible complications of an atrial septal defect (ASD).
Pulmonary hypertension, right heart failure and atrial arrhythmia.
Explain why pulmonary hypertension is rare in ASD.
The difference in pressures between the left and right atria is minimal so that not so much blood flows from left to right, and the effect on the pulmonary pressure will be low.
What percentage of the population has a patent foramen ovale (PFO)?
Why are most Asymptomatic?
20%.
Because the higher pressure in the left atrium causes functional closure of the flap valve.
What is a paradoxical embolism?
A transient increase in pressure in the right side of the heart causes opening of a patent foramen ovale and a pulmonary embolism to pass through to the systemic circulation.
Why is a VSD more severe than an ASD?
The difference in pressure between the two ventricles is greater, meaning there is a greater flow from left to right through the defect in a VSD. Increases pulmonary venous congestion.
What do patients with a VSD commonly present with? Why, and at what age?
Left heart failure due to the left heart working harder to maintain cardiac output in the lower volumes.
Usually present in infancy.
What is Eisenmenger syndrome?
When a patient has a left-to-right shunt (congenital heart defect) causing the pulmonary resistance and pressure to increase beyond that of the systemic circulation (due to remodelling). Means the shunt reverses direction, becoming right-to-left as right heart pressures increase. Patient becomes cyanotic.
What is coarctation of the aorta?
A narrowing of the aortic lumen in the region of the ligamentum arteriosus.
Give some complication of coarctation of the aorta.
Increased afterload leads to LV hypertrophy, weak femoral pulse, congestive heart failure, renal hypertension, volume overload, radial-radial delay.
What causes a congenital heart condition to be cyanotic?
When there is mixing of deoxygenated blood with the systemic, oxygenated, circulation so that this blood bypasses the lungs and lowers the oxygen saturation of the systemic circulation.
What is required for a cyanotic heart defect to occur?
A right to left shunt - requires a hole in the septum and distal obstruction to raise the pressure in the right side of the heart.
What causes tetralogy of fallot?
Abnormal development of the outflow portion of the inter-ventricular septum.
What are the 4 abnormalities in TOF?
- VSD
- Pulmonary stenosis
- RV hypertrophy
- Over-riding aorta
What is pulmonary atresia?
A lack of development of the tricuspid valve and right atrioventricular connection. Resulting in right to left shunt of entire venous return via an atrial septal defect.
Why do babies born with pulmonary atresia not die straight away?
Because the ductus arteriosus remains open for some time, allowing some flow to the lungs as the blood passes from the aorta to the pulmonary trunk.
May also have a ventricular septal defect which will also allow flow to the lungs.
Name 2 congenital heart defects that are neonatal emergencies.
Transposition of the great vessels.
Hypo plastic left heart.
What is transposition of the great arteries?
The aorta is attached to the right ventricle while the pulmonary trunk is attached to the left ventricle giving 2 unconnected circuits (pulmonary and systemic).
How are patients with transposition of the great vessels kept alive prior to surgery?
By giving drugs to keep the ductus arteriosus open - so there is some connection between the two circuits.
Or by making or enlarging any existing septal defects to allow bloods to mix and some oxygenated blood to enter the systemic system.
What is hypoplastic left heart syndrome?
Hypoplasia (underdevelopment) of the left ventricle and ascending aorta
Explain how patients with a hypoplastic left heart survive.
They usually have an atrial septal defect (patent foramen ovale) through which all the blood flows from the left atrium to the right, and enters the pulmonary trunk. A patent ductus arteriosus allows blood to flow into the aorta and supplies the systemic circulation.
What happens to the blood in pulmonary atresia?
Same as tricuspid atresia. Right to left shunt (usually through PFO), blood enters aorta but can enter the pulmonary circulation through a PDA.
In 100,000 births, how common is ASD?
67 / 100,000
How common is a VSD in 100,000 births?
150-350 VSDs
How common is a PDA in 100,000 births?
20-40 PDAs
How common is TOF in 100,000 births?
50 / 100,000 births
How common is transposition of the great vessels in 100,000 births?
40 / 100,000 births
How common is hypoplastic left heart syndrome in 100,000 births?
16-36 in 100,000 births
Which of the following are cyanotic heart defects: ASD, VSD, PDA, transposition of the great vessels, Eisenmenger Syndrome, TOF, coarctation of the aorta, pulmonary stenosis, aortic stenosis, tricuspid atresia, hypoplastic left heart syndrome, pulmonary atresia.
Transposition of the great arteries. Eisenmenger syndrome. TOF Tricuspid atresia Hypoplastic left heart syndrome. Pulmonary atresia.
How long is the average ventricular myocyte action potential?
300ms
What is the resting membrane potential of a ventricular myocyte?
-90mV
To what membrane potential does a ventricular myocyte depolarise during an action potential?
+30mV
What is the most negative membrane potential reached in a sino-atrial nodal cell?
-60mV
How long is a sino-atrial nodal action potential?
200ms
To what membrane potential does a sino-atrial nodal cell depolarise during an action potential?
+30mV
During stage 2 of a ventricular myocyte action potential, are potassium channels open or closed?
Open
Why is depolarisation by the funny current in sino-atrial nodal cells slow?
Because the funny channels are permeable to potassium as well as sodium
Why are sinoatrial-nodal action potentials known as slow response?
The upstroke of depolarisation is slightly less steep than a ventricular myocyte action potential
What is the main difference between cardiac and skeletal muscle in excitation-contraction coupling?
Cardiac muscle = calcium induced calcium release (L type calcium channels in membrane open due to membrane depolarisation, calcium binds calcium channels in SR and opens them).
Skeletal muscle = conformational change in SR calcium channels triggers their opening.
During cardiac muscle contraction, approximately what proportion of the calcium comes from the extracellular fluid and what proportion from the sarcoplasmic reticulum?
25% from ECF
75% from SR
What type of GPCR are alpha1 receptors alpha1 receptors on vascular smooth muscle?
Linked to Gq G-protein.
How many molecules of calcium bind calmodulin in smooth muscle contraction?
4
What is the action of activated calmodulin in smooth muscle contraction?
Binds to myosin-light-chain-kinase (MLCK) to activate it so that it can now use ATP hydrolysis to phosphorylate heads of myosin light chain to initiate cross bridge cycling.
What is the action of myosin light chain phosphatase (MLCP)?
What inhibits it?
MLCP removes the phosphate group from myosin light chain to terminate cross-bridge cycling and contraction in smooth muscle cells.
Inhibited by phosphorylation by PKC (in turn activated by DAG).
What mechanism inhibits myosin light chain kinase?
Binding of adrenaline to beta adrenoceptors results in PKA activation which Phosphorylates MLCK and inhibits it. Leads to smooth muscle relaxation.
What 3 things within the CVS does the autonomic nervous system regulate?
Heart rate, force of contraction and peripheral resistance
Where are the parasympathetic ganglions in the heart?
On the epicardial surface or within the heart walls at the SA and AV nodes only.
How does the parasympathetic nervous system act to slow heart rate?
Via release of ACh onto M2 receptors - Gi G-proteins. Increase potassium conductance (hyperpolarisation) and decrease cAMP production (decreases slope of pacemaker potential).
Also slows AV conduction velocity.
What parts of the heart does the cardiac accelerator nerve innervate?
A sympathetic nerve = SA node, AV node and myocardium.
What type of sympathetic adrenoreceptor is mainly present in the heart?
Beta1
What type of GPCR are beta1 receptors?
Coupled to Gs G-protein
In what 3 ways does the sympathetic innervation of the heart increase inotropy?
- Activation of PKA results in phosphorylation of calcium channels ( = increase calcium entry).
- Increased calcium entry results in build up of calcium stores in the SR so that subsequent contractions are more forceful.
- Increased sensitivity of contractile machinery to calcium
What is vasomotor tone?
The basal level of activity of the sympathetic nervous system at blood vessels - the basal level of vasoconstriction.
What is the most common adrenoceptors found at vessels?
Alpha1 adrenoceptors
In addition to alpha1 adrenoceptors in their vessels, which 3 tissue types also have beta2 adrenoceptors? And which single tissue has only beta2 adrenoceptors?
Liver, myocardium and skeletal muscle has both.
Coronary vessels have beta2 only.
What is the advantage of some tissues having beta2 adrenoceptors present in their vessels as well as alpha1?
Increases their response to circulating adrenaline. Beta2 results in active vasodilation by activation of PKA to open potassium channels and inhibit MLCK.
What is the most important stimulus for vasodilation?
Local metabolites - adenosine, K+, H+ and CO2
How are changes to the state of the CVS communicated to the brain?
Via sensory neurones from baroreceptors (in glossopharyngeal and vagus nerves).
Afferent neurones from the atrial volume receptors.
Name 3 sympathomimetics (adrenoceptors agonists) and when they are used.
Adrenaline - in cardiac arrest and anaphylactic shock.
Dobutamine - in cardiogenic shock (beta1 agonist) = increased inotropy.
Salbutamol - in asthma (beta2 agonist) = relaxation of bronchial smooth muscle.
Name 3 adrenoceptors antagonists and their uses.
Prazosin- hypertension (alpha1 antagonist)
Propranolol - angina and hypertension (beta1 and beta2 antagonist) = slowed HR and reduced inotropy.
Atenolol - angina and hypertension (beta1 antagonist).
What receptor is pilocarpine an agonist for?
What is used for?
M3 cholinergic receptor.
Used for treatment of glaucoma - constricts pupil allowing aqueous humour to drain.
What type of drug is atropine?
What is it used for?
A cholinergic receptor antagonist.
Used to dilate pupils, increase HR and dilate bronchioles.
Which cranial nerves does the parasympathetic nervous system originate from?
CNIII, VII, XI and X
Which thoracolumbar spinal nerves does the sympathetic nervous system originate from?
T1 - L2
What are the 2 co-transmitters released with noradrenaline at post-ganglionic sympathetic neurones?
NPY and ATP
At what stage of the ventricular action potential are calcium channels inactivated?
Stage 4 - repolarisation after the plateau
What type of calcium channel is responsible for the plateau stage?
L-type calcium channel
Which potassium channel type is responsible for the initial repolarisation of the ventricular action potential?
Voltage gated Ito channel = transient outward
What potassium channel type is responsible for full repolarisation during the cardiac action potential?
Delayed rectifier channels (Ik)
Why is depolarisation of the pacemaker potential slow?
Because the If funny current channels are also permeable to potassium ions, as well as sodium.
At what membrane potential are the funny channels activated?
More negative than +50mV
What is the proper name for funny current channels? Therefore what activates them?
HCN - hyperpolarisation-activated, Cyclic Nucleotide-gated channels.
Activated by hyperpolarisation of the membrane and cAMP.
Why is the sink-atrial node usually responsible for setting the rhythm of the heart?
Because it has the fastest rhythm / steepest pacemaker potential.
If the SA node was removed, what would take over as the rhythm setter?
AV node
If both nodes were removed, what would take over as the rhythm setter?
The purkinje fibres
Cardiac myocytes are joined structurally by ….. And electrically by ….. These are both found at the …….
Structurally by desmosomes.
Electrically by connexins of gap junctions.
Both found at the intercalated disk.
The actin filaments of smooth muscle are cross linked at attached to…..
Attached to dense bodies
Define ‘flow’ in terms of vessels.
The volume of fluid passing a given point per unit time (ml/min)
An increased pressure gradient along a vessel will do what to flow?
Increase flow
If there is no change to the pressure gradient along a tube, an increase in resistance will do what to flow?
Decrease flow
Define ‘velocity’ in the CVS.
The rate of movement of fluid particles along a tube (cm/sec)
What 3 things is resistance of a vessel dependent on?
- Viscosity of the blood
- Shear forces of vessel walls
- Vessel diameter
Give an equation link ing flow to pressure gradient and resistance.
Q = P / Res.
If flow remains the same along a vessel, but cross sectional area decreases, what will happen to velocity?
Velocity will increase
Give an equation linking flow to velocity and cross sectional area.
Q = Velocity X Cross Sectional Area (r^2)
Explain why the aorta has a very high velocity of blood compared with the capillaries despite the same flow.
Velocity is inversely proportional to the radius^2 of a vessel so that if radius doubles in size, the velocity decreases by 1/4. The aorta has a cross sectional area of about 2.5cm^2 whereas that of the capillaries is 4500cm^2. Therefore the overall cross sectional area of the capillaries is much larger and much slower than the aorta.
Describe laminar flow.
A gradient of velocity of blood from the centre of the vessel, where velocity is highest, to the edge of the vessel, where fluid is stationary.
Describe turbulent flow.
The velocity gradient from the centre of periphery of a vessel breaks down and fluid tumbles over. Causes an increase in flow resistance.
Generally, what 3 things increase the chances of turbulence?
- Irregular lumen
- High velocity of blood
- High viscosity of blood
How is turbulence detected?
By auscultation - heart as a Bruit
Define viscosity.
The extent to which fluid layers slide over one another.
If all else remains the same, what will happen to flow if viscosity is increased?
Flow will decrease
What 3 things is resistance to flow determined by?
Give an equation linking these together.
- Vessel diameter
- Vessel length
- Blood viscosity
Resistance = (length of vessel X viscosity of flood) / vessel diameter (r^4)
Is viscosity of blood higher in the capillaries or aorta?
Aorta - where sheer stresses are low
Give 3 scenarios where the viscosity of blood would be increased.
Hyper-proteinaemia.
Infection - increase white blood cells in the blood.
Fluid loss / dehydration.
What relationship does viscosity have with average velocity of laminar flow?
Increased viscosity slows the central layer of laminar flow and therefore the average velocity of flow decreases. (Inversely proportional)
If you have a 2 fold increase in the radius of a vessel lumen, but nothing else changes, what will happen to the resistance?
Decreases by 16 fold (2^4)
Define resistance.
What must be overcome to push blood through a vessel and create flow.
Give Poiseuille’s law.
Q = (P X r^4) / viscosity X tube length
Explain why a very small decrease in radius dramatically decreases flow.
According to Poiseuille’s law, flow is proportional to radius^4.
What factor has the dominant influence on resistance and flow?
Vessel radius
Give an equation linking pressure to resistance and flow.
Pressure = flow X resistance
If 2 tubes are connected in series, the resistance is…
The sum of the 2 resistances from each tube added together = massive increase.
