What is isovolumetric contraction.
Ventricular contraction when all valves are closed. This increases ventricular pressure but as the valves are closed the volume remains unchanged.
What produces the first heart sound?
Closing of the mitral valve.
What causes the mitral valve to close?
When LVp exceeds LAp. Just before ventricular isovolumetric contraction.
Wave of depolarisation arrives, Ca2+ channels open.
LVp>LAp and the mitral valve closes.
LVp rises, isovolumetric contraction, LVp>aortic p.
Aortic valve opens and ejection begins.
What produces the second heart sound?
Closing of the aortic valve.
LVp decreases and there is a phase of reduced ejection. LVp is less than aortic pressure and the aortic valve closes: isovolumetric ventricular relaxation. LVp is less than LAp and mitral valve opens - ventricles fill with blood. Atria contract - atrial booster. LVp > LAp and mitral valve closes.
What is the duration of systole?
What is the duration of diastole?
What is end systolic volume?
The volume of blood remaining in the LV following systole.
The volume of blood in the ventricles just before contraction (EDV).
The pressure against which the heart must work to eject blood in systole.
The inherent strength and vigour of the heart’s contraction during systole.
Myocardial ability to recover it’s original shape after systolic stress.
How easily a chamber of the heart expands when it is filled with blood (C=ΔV/ΔP).
Define diastolic distensibility.
The pressure required to fill the ventricle to the same diastolic volume.
A force that must be overcome to push blood through the circulatory system.
What is the basic principle of Starling’s law of the heart?
Increased EDV = increased SV.
Explain Starling’s law.
The greater the EDV, the greater the sarcomeres are stretched and the more forceful the contraction.
With relation to Starling’s law, what is the effect of an increased venous return?
EDV will increase and so SV increases and so Cardiac output also increases as CO=SVxHR.
Give the equation for stroke volume.
Give the equation for cardiac output.
Define cardiac output.
The volume of blood each ventricle pumps per unit time.
Give the equation for mean arterial pressure.
MAP = DP + 1/3(SP-DP).
SP - systolic pressure, DP - diastolic pressure
Give the equation for pulse pressure.
Give the equation for blood pressure.
What is Poiseuille’s equation?
What is Ohm’s law?
What are the principle vessels of resistance?
What do arterioles respond to?
Blood pressure changes. Local, neural and hormonal factors.
Name 2 local factors that result in vasoconstriction.
Endothelin, internal BP.
Name 5 local factors that result in vasodilation.
Hypoxia, NO, K+ (accumulate from AP), CO2, H+, adenosine.
What neural factors result in vasoconstriction?
Sympathetic nerves that release noradrenaline.
What neural factors result in vasodilation?
Name 3 hormonal factors that result in vasoconstriction.
Angiotenisn 2, ADH, Adrenaline (binds to alpha-adrenergic receptors in smooth muscle).
Name 2 hormonal factors that result in vasodilation.
Atrial natriuretic peptide, Adrenaline (binds to beta2 receptors).
What is myogenic auto-regulation of blood flow?
An intrinsic mechanism in smooth muscle blood vessels. If BP increases the vessel constricts. This is important in regulating blood flow.
Myogenic auto-regulation of blood flow: What is the response to an increase in BP?
Increased BP will result in vasoconstriction and so blood flow decreases.
Myogenic auto-regulation of blood flow: What is the response to a decrease in BP?
Decreased BP will result in vasodilation and so blood flow increases.
What is hyperaemia?
An increased blood flow to tissues.
What is the cause of active hyperaemia?
When blood flow increases due to an increase in metabolic activity.
- Increased metabolic activity = decreased O2 and increased metabolites = arteriolar dilation = increased blood flow.
What is the cause of reactive hyperaemia?
When blood flow increases following occlusion to arterial flow.
Describe excitation-contraction coupling.
- Na+ depolarises membrane.
- A small amount of Ca2+ is released from T tubules.
- Ca2+ channels in sarcoplasmic reticulum open.
- Ca2+ flows into cytosol. Cytosolic Ca2+ conc raised.
- Ca2+ binds to troponin C, this pulls tropomyosin and exposes the myosin binding site on actin.
- Cross bridge cycling begins.
- After depolarisation, Ca2+ is returned to SR. K+ outflow = repolarisation.
What effect does myocardial contraction have on the A-band of a sarcomere?
No effect, it stays the same length.
What effect does myocardial contraction have on the I-band and H-zone of a sarcomere?
They get shorter.
Describe actin (thin filament).
A globular protein, single polypeptide. It polymerises with other actin monomers to form a double stranded helix. Together they form F actin.
Describe myosin (thick filament).
2 heavy polypeptide chains and 4 light chains. The myosin heads have 2 binding sites; one for actin and one for ATP.
An elongated molecule made of 2 helical peptide chains.
What is the function of troponin I?
Troponin I, together with tropomyosin, inhibits actin and myosin binding.
What is the function of troponin T?
Troponin T binds to tropomyosin.
What is the function of troponin C?
Troponin C has a high affinity for Ca2+. TnC drives away TnI and so allows cross bridge formation.
Name 3 effectors in circulation control.
- Blood vessels - vasoconstrict/dilate and effect TPR.
- The heart - can affect rate or contractility.
- Kidneys - regulates blood volume and fluid balance.
Where are baroreceptors located?
Aortic arch and carotid sinus.
What activates baroreceptors?
Baroreceptors contain stretch receptors that respond to pressure.
Are atrial baroreceptors involved in short-term or long-term regulation of BP?
Short-term. (Cardiopulmonary = long-term).
Where central chemoreceptors located?
In the medulla oblangata.
What do central chemoreceptors respond to?
Changes in pH/(H+).
Increased PaCO2 increases H+ and so decreases pH.
Increased PaCO2 results in vasodilation.
What is the ligamentum teres a remnant of?
The umbilical vein.
What is the ligamentum venosus a remnant of?
The ductus venosus.
Briefly describe foetal circulation.
Maternal circulation - umbilical vein (oxygenated blood) - ductus venosus - IVC - RA - LA/RV - aorta - umbilical artery (deoxygenated blood) - maternal circulation.
What layer of the tri-laminar disc forms the cardiovascular system?
What does the first heart field produce?
The left ventricle.
What does the second heart field produce?
The right ventricle, atria and outflow tracts.
What are the 3 stages of heart formation?
- Formation of primitive heart tube.
- Cardiac looping.
- Cardiac septation.
Describe what happens in the formation of the primitive heart tube.
Two endocardial tubes form (day 19). The tubes fuse together and the heart beats (day 22).
Describe what happens in cardiac looping.
Nodes secrete nodal, this circulates to the left due to ciliary movement. Nodal causes a cascade of transcription factors that transduce looping.
Describe what happens in cardiac septation.
Endocardial cushions form. Fuse at mid-line to form atrio-ventricular septum. Muscular ridge in the floor of the primitive ventricle migrates to endocardial cushions forming interventricular septum.
What does the sinus venosus form?
The coronary sinus and RA.
What does the primitive atrium form?
RA and LA.
What does the primitive ventricle form?
Forms most of LV.
What does the bulbus cordis form?
Part of the ventricles.
What does the truncus arteriosus form?
The aorta and pulmonary trunk.
What do the 1st and 2nd aortic arches form?
Minor vessels in the head.
What does the 3rd aortic arch form?
The common carotid arteries.
What does the left and right 4th aortic arch form?
Left - aorta. Right - Right subclavian artery.
What does the 5th aortic arch form?
There is no 5th arch!
What does the left and right 6th aortic arch form?
Left - left pulmonary artery and ductus arteriosus. Right - right pulmonary artery.
What does the 7th segmental aortic arch form?
Left and right subclavian arteries.
What does the dorsal aortae form?
Left dorsal aortae - descending aorta. Right dorsal aortae - part of right subclavian artery.
What are chronotropic effects?
Those that change the heart rate. Positive chronotropic = increased heart rate.
What are inotropic effects?
Those that alter the force of muscular contractions.
What affect does parasympathetic stimulation have on heart rate?
Decreases heart rate (-ve chronotropic). Cardiac output therefore decreases with parasympathetic stimulation. (CO=HRxSV).
What affect does sympathetic stimulation have on force of contraction?
Increases force (+ve inotropic).
What pump maintains the negative resting potential of a membrane?
What is the purpose of the Nernst equation?
It is used to determine a membranes potential.
Give the Nernst equation.
E = 60log(conc outside/conc inside)
What membrane channels are responsible for the plateau period in the cardiac AP?
Voltage gated Ca2+ ‘slow’ channels.
Briefly describe the cardiac action potential in 5 steps.
- Na+ channels open; influx of Na+ into cell; depolarisation.
- When the Na+ channels close, a small number of K+ leave the cell resulting in partial repolarisation.
- Ca2+ channels open and there is Ca2+ inflow. K+ channels are also open and there is K+ outflow. This results in the plateau period.
- Ca2+ channels close and K+ channels remain open. K+ leaves the cell resulting in repolarisation.
- Maintaining the resting potential (approx -90mV). Na+ inflow, K+ outflow.
Where is the SAN located?
In the RA under the crista terminalis.
Briefly describe the electrical conduction pathway in the heart.
- The SAN generates an electrical impulse.
- This generates a wave of contraction in the atria.
- Impulse reaches AVN.
- There is a brief delay to ensure the atria have fully emptied.
- The impulse then rapidly spreads down the Bundle of His and Purkinje fibres.
- The purkinje fibres then trigger coordinated ventricular contraction.
Why is there rapid conduction in the bundle of his and purkinje fibres?
- The fibres have a large diameter.
2. There is high permeability at gap junctions.
What is the function of the refractory period?
- It prevents excessively frequent contractions.
2. It allows time for the atria to fill.
What does the P wave on an ECG represent?
Atrial depolarisation. Duration is less than 0.12s.
What does the QRS complex on an ECG represent?
Ventricular depolarisation. Duration is 0.08-0.1s.
What does the T wave on an ECG represent?
What might an elevated ST segment be associated with?
ECG: where would you place lead 1?
Right arm (-ve) to left arm (+ve).
ECG: where would you place lead 2?
Right arm (-ve) to left leg (+ve).
ECG: where would you place lead 3?
Left arm (-ve) to left leg (+ve).
What is Einthoven’s triangle?
An imaginary formation of the 3 limb leads in a triangle shape.
ECG: where would you place lead aVR?
Left arm and left leg (-ve) to right arm (+ve).
ECG: where would you place lead aVF?
Right arm and left arm (-ve) to left leg (+ve).
ECG: where would you place lead aVL?
Right arm and left leg (-ve) to left arm (+ve).
ECG chest leads: In which intercostal space would you place V1 and V2?
The 4th intercostal space. V1 is right of the sternum and V2 in left.
ECG chest leads: In which intercostal space would you place V3-V6.
The 5th intercostal space. V3 is left of the sternum, V4 is in the mid-clavicular line, V5 is left of V4 and V6 is under the left arm.
What are the average systolic and diastolic pressures for the pulmonary circulation?
25 and 10 mmHg.
What are the average systolic and diastolic pressures for the systemic circulation?
120 and 80 mmHg.
Why might someone with liver injury experience prolonged bleeding time?
Because the liver produces clotting factors.
What is exposed if you damage the endothelium of a vessel?
Underlying connective tissue and collagen.
What is the role of vWF?
vWF binds to collagen and platelets bind to vWF.
What happens in platelet activation?
The change shape: smooth to spiculated. This increases their surface area. New platelets adhere to old ones = platelet aggregation. This forms a platelet plug.
What do activated platelets synthesise?
What is the function of Thromboxane A2 (TXA2)?
It leads to further platelet aggregation.
What are the platelet receptors for fibrinogen?
glycoprotein IIb/IIIa. Fibrinogen forms ‘bridges’ between platelets.
What does an undamaged endothelium release in order to prevent platelet activation in undamaged areas?
Prostacyclin (inhibits platelet aggregation) and NO (inhibits platelet adhesion).
What are platelets made from? and where are they made?
In the bone marrow from megakaryocytes.
In haemostasis what is prothrombin converted into?
Give 3 functions of Thrombin.
- Converts fibrinogen into fibrin.
- Activates factor XIII into XIIIa.
- Has a positive feedback effect resulting in further thrombin production.
What is the essential component of a blood clot?
Briefly describe the Fibrinolytic system.
Plasminogen is converted into plasmin. Plasmin cuts the fibrin at various places leading to the formation of fragments.
What is the purpose of the fibrinolytic system?
It acts to prevent blood clots from growing and becoming problematic.
What is the structure of Hb?
2 alpha and 2 beta chains. 4 haem groups.
Describe the composition of blood.
Plasma - 55%.
Cellular - 45% - RBC: 44%, WBC: 1%.
Does blood flow to the heart occur during diastole or systole?
What does the left coronary artery divide into?
The left anterior descending, and the circumflex.
Why is the O2 saturation in coronary venous blood very low?
O2 extraction by the heart muscle is very high.
What surface of the heart does the right coronary artery supply?
The inferior surface (underside) of the heart.
What is released upon cell activation and contains a high concentration of a molecule that acts as an agonist at the platelet P2Y12 receptor?
Platelet dense granules.
What valve prevents high pressures developing in the jugular veins during ventricular systole?
What is the normal duration for the PR interval?
What ECG lead yields complexes that are normally inverted compared to the anterior and inferior leads?
Is there a point in the cardiac cycle when both atrial and ventricular diastole occur together?
Yes: when the ventricles are relaxing and the atria are filling (before atrial contraction).
Why does an increase in LVEDV signify heart failure?
Heart failure is the inability to pump blood out of the heart. There is blood remaining at the end of systole. The blood therefore accumulates and so LVEDV increases.
Which pressure is most likely to increase in left sided heart failure?
Which pressure is most likely to decrease in left sided heart failure?
Mean aortic pressure.
Less blood is being pumped into the aorta
What is stenosis?
Which pressure is most likely to increase in mitral valve stenosis?
Left atrial end-systolic pressure.
What does it mean if a heart valve is incompetent?
It is regurgitant.
Which pressure is most likely to increase when the aortic valve is incompetent?
Left ventricular end-diastolic pressure.
Pulmonary oedema is a sign of what?
Left heart failure.
What can severe pulmonary hypertension cause?
Right heart failure.
The heart has to pump harder to get blood into the pulmonary circulation due to an increased afterload.
Shortness of breath, severe peripheral oedema and ascites after a heart attack can indicate what?
What is ascites?
Accumulation of fluid in the peritoneal cavity, this can cause abdominal swelling.
How long is the PR interval on an ECG?
What does the PR interval represent?
The slow conduction between the AVN and the His-Purkinje system.
Diastole: what is diastasis?
When LVp = LAp. Net movement of blood is zero. This is the time between ventricular suction and atrial contraction.
What branch does the right coronary artery give off as it reaches the inferior border of the heart?
The right marginal branch.
What artery does the RCA anastomose with on the diaphragmatic surface of the heart?
The circumflex artery.
What does the LAD anastomose with on the diaphragmatic surface of the heart?
The posterior inter-ventricular branch of the RCA.
Where is the coronary sinus found?
Between the LA and LV - left atrio-ventricular sulcus.
What does the coronary sinus drain into?
What artery arises from the RCA in 90% of hearts, the circumflex in 30% and in 20% arises from both the RCA and circumflex?
The posterior inter-ventricular branch.
What equation explains why small changes in the diameter of a blood vessel have a great effect on the resistance to flow of a fluid through that vessel?
Poiseuille’s equation. Q=r^4.
What is the role of fibrinogen in platelet aggregation?
It forms cross-links between aggregating platelets.
Give 2 reasons why the liver is important in clotting.
- The liver produces many clotting factors.
- The liver produces bile salts that are needed for vitamin K absorption. Vitamin K is needed for clotting factor production.
When are the platelet receptors for fibrinogen exposed?
During platelet activation.
Which of the ABO blood groups is recessive?
O, A and B are co-dominant.
Why is the O blood group a universal donor?
It has no A or B antigens.
What are the two ways of determining someones ABO blood group?
- Test using antibodies.
2. Test for the presence of antibodies against A or B antigens.
Describe how testing for the presence of antibodies against A or B antigens will determine someones blood group?
The presence of antibodies in the blood will indicate that this person does not have these antigens on their RBC’s. For example, if a persons blood is found to contain antibodies against the B antigen then they can’t be of the AB or B blood groups.
Describe how testing using antibodies will determine someones blood group?
If the antibodies bind it indicates the presence of a specified antigen. For example, if antibodies against the B antigen bind to the patients RBC then the person must be of either the AB or B blood groups.
What are antigens are part of the Rhesus blood group system?
C, D and E.
D is the most important
What problems can arise if a pregnant lady is found to be rhesus D negative?
If exposed to D RBC’s the lady will have antibodies against the D antigen. The antibodies can cross the placenta and cause haemolysis of the babies red blood cells. This can result in in-utero death.
What can be given to rhesus D negative mothers to prevent sensitisation?
Describe the arterial baroreceptor reflex in response to an increase in blood pressure.
- Increased parasympathetic outflow to the heart means contractility and heart rate are reduced and so cardiac output is reduced: CO=HRxSV.
- Decreased sympathetic outflow to the arterioles results in vasodilation and so TPR is reduced.
- BP=COxTPR and so blood pressure is lowered.
Describe the arterial baroreceptor reflex in response to a decrease in blood pressure.
- Increased sympathetic outflow to the heart means contractility and heart rate are increased and so cardiac output is increased: CO=HRxSV.
- Increased sympathetic outflow to the arterioles results in vasoconstriction and so TPR is increased.
- BP=COxTPR and so blood pressure is increased.
What phase of the cardiac action potential coincides with diastole?
What part of the ECG does the plateau phase of the cardiac action potential coincide with?
Give 4 factors that affect the gating of ion channels.
Voltage, drugs, hormones, temperature.
What is Virchow’s triad?
It describes 3 categories thought to contribute to thrombosis.
What are the 3 categories of Virchow’s triad?
- Stasis of blood flow.
- Endothelial injury.
- Increased coagulation ability.
A decrease in blood flow to a tissue.
No blood flow to a tissue - tissue death.
Explain the formation of fluid exudate in inflammation.
Chemical mediators cause vasodilation of vessels and an increase in permeability.
What are the roles of lymphatics in acute inflammation?
Lymphatics drain exudate and carry antigens.
What happens in phase 4 of the cardiac action potential?
Pacemaker potential - Na+ inflow and slowing of K+ outflow. Slow depolarisation begins = innate contractility.
Where is Ca2+ released from in excitation contraction coupling?
The T tubules and the sarcoplasmic reticulum.
What is the resting potential of the SA node?
-55 to -60 mV.
How do central chemoreceptors respond to an increase in PaCO2?
Why do central chemoreceptors stimulate vasoconstriction in response to an increase in PaCO2?
They act to counter the affect of CO2 as a vasodilator and so maintain blood flow to tissues.
What reaction does adenyl cyclase catalyse?
The conversion of ATP into cAMP.
How do muscarinic M2 receptors cause a decrease in cAMP?
They inhibit adenyl cyclase.
What 2 channels are closed during the refractory period in a cardiac action potential?
Fast Na+ and Ca2+ channels.
What surface of the heart does the RCA supply?
What is the normal duration of the PR interval?
What would an absent P wave on an ECG be a sign of?