Cardiac Cycle Flashcards
Blood flow equation
Change in pressure along the vessel / resistance in the vessel
Factors increasing blood pressure
Increased cardiac output
Increased stroke volume
Increased heart rate
Increased peripheral resistance
Increased aortic elasticity
Activation of renin-angiotensin-aldosterone system
Sympathetic nervous system activation
How does Sympathetic nervous system activation increase blood pressure
Increased heart rate
Ionotropy- heart muscles to beat or contract with more power
Peripheral vascular resistance
How does arterial vasoconstriction increase blood pressure
Increased systemic vascular resistance
How does venous vasoconstriction increase blood pressure
Increased stoke volume so increased cardiac output
Factors controlling vasodilation
Parasympathetic activation
Endothelial factors: ACh, ADP/ATP, nitric oxide
Increased temperature
Acidosis eg lactate, hypercapnoea
Histamine
Prostaglandins
Factors controlling vasoconstriction
Sympathetic activation
Endothelial factors: microtrauma, hypoxia -> endothelin-1 release
Decreased temperature
Adrenaline/noradrenaline
Renin-angiotensin-aldosterone system activation
When does venous return increase
During respiratory inspiration due to a decrease in right atrial pressure
Opposite during expiration
Cause of second heart sound
A decrease in ventricular pressure causes the aortic and pulmonary valves to close
End diastolic volume
The volume of blood in the ventricles following diastole
Reached immediately after atrial contraction and immediately before the AV valves close
Normal value for EDV
120 ml
Factors influencing EDV
Ventricular filling pressures
Heart rate
Ventricular compliance
Right ventricular filling pressure
Central venous pressure
Left ventricular filling pressure
Pulmonary wedge pressure
Central venous pressure
Pressure of vena cava immediately before filling right atrium
Stroke volume
Volume of blood pumped by left ventricle per beat
Typical stroke volume
70 ml
End-systolic volume
Volume of blood in ventricles following ventricular systole
Normal ESV value
50 ml
Factors affecting stroke volume
Heart size
Contractility
Preload (end-diastolic volume)
Afterload (ejection pressure during ventricular diastole)
Exercise
pH changes
Electrolyte imbalances
Drugs (e.g. calcium channel blockers)
Increased inotropy
Sympathetic nervous system stimulation
Low extracellular sodium
High extracellular calcium
Adrenaline, dobutamine, dopamine, digoxin, glucagon, levothyroxine
Decreased inotropy
Hypoxia
Acidosis, eg hypercapnoea
Heart failure
Beta-blockers, anaesthetics eg lidocaine, anti-arrhythmogenic eg flecainide
Preload
Determined by end-diastolic volume
the load present before LV contraction has started
• ventricular stretch at the end of diastole
• affecting factors- Venous blood pressure and the rate of venous return
• Occurs during diastole
• Depends on amount of ventricular filling
• Preload is a volume
Factors increasing preload
Increased blood volume
Gravity
Increased venous tone
Frank-starling law
As EDV increases, stroke volume increases due to increased cardiomyocyte stretch and therefore a more forceful contraction
This is because the amount of tension (force of muscle contraction during systole) depends on the resting length of the sarcomere, which is dependent on the amount of blood that fills the ventricles during diastole. The length of the sarcomere determines the amount of overlap between the actin and myosin filaments and so the number of cross-bridges that can form. Low end diastolic volume reduces sarcomere stretching, so fewer myosin heads bind to actin- leading to weaker contraction. However, too much sarcomere stretching prevents optimal overlapping between actin and myosin also reducing the force of contraction.
Optimal length of sarcomere- frank starling law
2.2um
Afterload
• the pressure that the chambers of the heart must generate in order to eject blood out of the heart
• Affected by systemic vascular resistance and and pulmonary vascular resistance
• Occurs during systole
• Depends on arterial blood pressure and vascular tone
• Afterload is a pressure
Factors affecting afterload
Blood pressure
Cardiac output
Systemic vascular resistance
Left ventricular volume
Aortic vessel pressure
Aortic valve resistance
Where does calcium bind to within the troponin complex
Troponin C
What effect does ANP have on blood vessels in the kidney
Vasodilation of the afferent arterioles and vasoconstriction of the efferent arterioles
ANP is released by the atria in response to increased ECF volume stretching the atria. It acts to increase GFR,which increases sodium and water excretion via the kidney
Actions of ANP (atrial natriuretic peptide)
lowersblood pressure, primarily by vasodilation and the inhibition of sodium reabsorption by the kidney, the latter having a diuretic effect.
Increased natriuresis
Decreased vasoconstriction in response to stimuli
Inhibition of renin and ADH
Lowering of systolic blood pressure
Neprilysin inhibitors (sacubitril/valsartan)
Target the endopeptidase inhibitors responsible for breaking down ANP
Treatment for Advanced, treatment-refractory heart failure
Mean arterial pressure
Arterial diastolic pressure/ (1/3 * pulse pressure)
Eg 140/80 mmHg
80/(1/3* 140-80) = 100mmHg
Resting membrane potential
-90 mV
How long does each cardiac action potential last roughly
200-400 ms
Phase 0- depolarisation
An action potential steadily increases the membrane potential of a cardiomyocyte
When the membrane potential reaches -70mV (the threshold value), it triggers the opening of Na+ channels in the membrane
This leads to rapid influx of Na+ into the cell, leading to a sharp rise in membrane potential (depolarisation)
Some L-type Ca2+ channels also open, so Ca2+ also moves into cell
Phase 1- early repolarisation
Once membrane potential reaches +40mV, Na+ channels close
Simultaneously, K+ channels open , leading to efflux of K+ out of the cell
Actions causes a slight decrease in membrane potential
Phase 2- plateau
K+ channels remain open , leading to continued efflux of K+ ions
Ca2+ channels also open, leading to influx of Ca2+
Ca2+ and K+ movement counteract each other- leading to a plateau
Phase 3- rapid repolarisation
Ca2+ channels close but K+ channels remain open with increasing channel permeability
Efflux of K+ causes rapid decrease in membrane potential
Phase 4- resting potential
Na+/K+ pump restores membrane potential to -90mV by moving 3 Na+ out and 2 K+ in
Also leaky K+ and Na+ channels which help to restore membrane potential
Why is the pacemaker current referred to as the ‘funny’ current
Mixed Na+/K+ current instead of only one ion type
Activated by hyperpolarisation (rather than depolarisation)
Very slow kinetics compared with other currents
Key differences between pacemaker cells and other cardiomyocytes
Phase 4 depolarisation
Absence of fast sodium channels, phase 0 mediated by sodium channels
Slower action potential upstroke with a lower amplitude
Pacemaker current
Mixture of Na+ and K+ current which is activated by hyperpolarisation at low voltages (around -60/-70 mV)
At end of each SAN action potential, membrane potential decreases due to repolarisation
Once threshold is reached, funny current is activated (phase 4 depolarisation)
Leads to inward current of Na+/K+ which restarts diastolic depolarisation phase
Provides automaticity for pacemaker cells as occurs at end stage, allowing continuous generation of action potentials
Reactive hyperaemia
Vasodilation and transient increase in blood flow that occurs n response to tissue ischaemia as occurs in coronary thrombosis, tissue hypoxia and metabolic waste accumulation
Level of blood flow after vessel occlusion is greater than before
In which blood vessel is there the largest fall in blood pressure and velocity
Arterioles to ensure blood slows down before entering capillaries to allow for optimal oxygen exchange
Which condition causes circulatory shock due to reduced venous return
Haemorrhage due to a reduced circulating volume and so reduced mean systemic filling pressure
Signs of circulatory shock
Weak pulse
Rapid heartbeat
Pale skin
Mean arterial pressure equation
[(Diastolic blood pressure x 2) + systolic blood pressure] / 3
Stages of cardiac cycle
Mid to late diastole
Systole
Early diastole
Diastasis
when the pressure in the atria and ventricular are the same
• filling temporarily stops.
Mid to late diastole
- left atrium and ventricle are both relaxed, but atrial pressure is slightly higher than ventricular pressure because the atrium is filling with blood that is entering from the veins.
- AV valve is held open by this pressure difference, and blood entering the atrium from the pulmonary veins continues on into the ventricle
- aortic valve is closed because the aortic pressure is higher than the ventricular pressure- Throughout diastole, the aortic pressure is slowly decreasing because blood is moving out of the arteries and through the vascular system.
- ventricular pressure is increasing slightly because blood is entering the relaxed ventricle from the atrium, thereby expanding the ventricular volume.
- Near the end of diastole, the SA node discharges and the atria depolarize, as signified by the P wave of the ECG.
- Contraction of the atrium causes an increase in atrial pressure- increased atrial pressure forces a small additional volume of blood into the ventricle, sometimes referred to as the “atrial augmentation.”
- end of ventricular diastole, so the amount of blood in the ventricle at this time is called the end-diastolic volume (EDV).
Which valves are open/closed during mid to late diastole
AV valve open
Semi-lunar valves closed
Atrial augmentation/kick
Contraction of the atrium causes an increase in atrial pressure- increased atrial pressure forces a small additional volume of blood into the ventricle
End-diastolic volume
end of ventricular diastole, so the amount of blood in the ventricle at this time is called the end-diastolic volume (EDV).
Systole
- From the AV node, the wave of depolarization passes into and throughout the ventricular tissue—as signified by the QRS complex of the ECG—and this triggers ventricular contraction.
- As the ventricle contracts, ventricular pressure increases rapidly; almost immediately, this pressure exceeds the atrial pressure.
- This change in pressure gradient forces the AV valve to close; this prevents the backflow of blood into the atrium.
- Because the aortic pressure still exceeds the ventricular pressure at this time, the aortic valve remains closed and the ventricle cannot empty despite its contraction. For a brief time, then, all valves are closed during this phase of isovolumetric ventricular contraction. Backward bulging of the closed AV valves causes a small upward deflection in the atrial pressure wave.
- This brief phase ends when the rapidly increasing ventricular pressure exceeds aortic pressure.
- The pressure gradient now forces the aortic valve to open, and ventricular ejection begins.
- The ventricular volume curve shows that ejection is rapid at first and then slows down.
- The amount of blood remaining in the ventricle after ejection is called the end-systolic volume (ESV).
- As blood flows into the aorta, the aortic pressure increases along with the ventricular pressure. Throughout ejection, very small pressure differences exist between the ventricle and aorta because the open aortic valve offers little resistance to flow.
- Note that peak ventricular and aortic pressures are reached before the end of ventricular ejection; that is, these pressures start to decrease during the last part of systole despite continued ventricular contraction. This is because the strength of ventricular contraction diminishes during the last part of systole.
- This force reduction is demonstrated by the reduced rate of blood ejection during the last part of systole.
- The volume and pressure in the aorta decrease as the rate of blood ejection from the ventricles becomes slower than the rate at which blood drains out of the arteries into the tissues.
isovolumetric ventricular contraction
aortic pressure still exceeds the ventricular pressure at this time, the aortic valve remains closed and the ventricle cannot empty despite its contraction. For a brief time, then, all valves are closed during this phase of isovolumetric ventricular contraction. Backward bulging of the closed AV valves causes a small upward deflection in the atrial pressure wave.
end-systolic volume (ESV).
The amount of blood remaining in the ventricle after ejection
Early diastole:
- As the ventricles relax, the ventricular pressure decreases below aortic pressure, which remains significantly increased due to the volume of blood that just entered. The change in the pressure gradient forces the aortic valve to close. The combination of elastic recoil of the aorta and blood rebounding against the valve causes a rebound of aortic pressure called the dicrotic notch.
- The AV valve also remains closed because the ventricular pressure is still higher than atrial pressure. For a brief time, then, all valves are again closed during this phase of isovolumetric ventricular relaxation.
- This phase ends as the rapidly decreasing ventricular pressure decreases below atrial pressure.
- This change in pressure gradient results in the opening of the AV valve.
- Venous blood that had accumulated in the atrium since the AV valve closed flows rapidly into the ventricles.
- The rate of blood flow is enhanced during this initial filling phase by a rapid decrease in ventricular pressure. This occurs because the ventricle’s previous contraction compressed the elastic elements of the chamber in such a way that the ventricle actually tends to recoil outward once systole is over. This expansion, in turn, lowers ventricular pressure more rapidly than would otherwise occur and may even create a negative (subatmospheric) pressure. Thus, some energy is stored within the myocardium during contraction, and its release during the subsequent relaxation aids filling.
isovolumetric ventricular relaxation.
The AV valve also remains closed because the ventricular pressure is still higher than atrial pressure. For a brief time, then, all valves are again closed during this phase of isovolumetric ventricular relaxation.
- This phase ends as the rapidly decreasing ventricular pressure decreases below atrial pressure.
dicrotic notch.
The combination of elastic recoil of the aorta and blood rebounding against the valve causes a rebound of aortic pressure
pressure in right ventricle to pump blood into lungs
34/10 mmHg
end-diastolic pressure of left ventricle
0 mmHg
pressure in atria
0-5 mmHg
Percentage ejection of blood from left ventricle for females
60-65%
Why is percentage ejection from left ventricle higher for females than males
Needed for fetal circulation
Percentage ejection of blood from left ventricle for males
50-55%
How to calculate max heart rate
Males: 220 - age in years = maximum heart rate
Females: 200 - age in years = max heart rate
First heart sound
When AV valve closed
Second heart sound
When semilunar valve closed
Third heart sound
Increase volume of blood within the ventricle
Slushing in
Caused by turbulent flow into the ventricles and detected near end of first one third of diastole (rapid ventricular filling)
Fluid backing up, as in cardiac failure
Fourth heart sound
Just after atrial contraction at the end of diastole and immediately before S1
A stiff wall
With the atrial systole
Non compliant ventricles
Sliding filament model
Sarcomeres within myofibrils shorten as the Z discs are pulled closer together
1. An action potential arrives- depolarisation of the membrane by Na+, causing Ca2+ to diffuse into the neurone
2. The Ca2+ causes vesicles containing ACh to fuse with the presynaptic membrane and release ACh by exocytosis
3. ACh diffuses across the synoptic cleft and binds to receptors in the sarcolemma, causing Na+ channels to open
4. Na+ diffuse into the sarcolemma, depolarising the membrane and generating an action potential that spreads down the T-tubules
5. L-type Ca2+ channels open and trigger Ca2+ diffuse out of the sarcoplasmic reticulum into the cytosol
6. This trigger Ca2+ binds to and opens ryanodine receptor Ca2+ channels in the sarcoplasmic reticulum membrane
7. Ca2+ flows into the cytosol, increasing the Ca2+ concentration
8. Ca2+ bind to troponin (TnC) molecules, stimulating them to change shape. This causes troponin and tropomyosin proteins to change position on the actin filaments, exposing myosin-binding sites.
9. The globular heads of the myosin molecules bind with these sites, forming cross-bridges between the two filaments after linkage of calcium and TnC, and deactivation of tropomyosin and TnI
10. The formation of cross-bridges causes the myosin heads to spontaneously bend (releasing ADP and Pi) pulling the actin filaments towards the centre of the sarcomere (i.e. closer together- 10nm) - power stroke
11. ATP binds to the myosin head, producing a change in shape that causes the myosin heads to be released from the actin filaments
12. ATPhydrolase hydrolyses ATP to ADP and Pi which causes the myosin head to cock back to its original position
13. The myosin head can then bind to new binding sites on the actin closer to the Z disc. The process repeats until the muscle is fully contracted
14. Later on, Ca2+-ATPase pumps return Ca2+ to the sarcoplasmic reticulum
15. Ca2+-ATPase pumps and Na+/Ca2+ exchangers remove Ca2+ from the cell
16. Membrane is depolarised when K+ exits to end the action potential
Troponin
• I: with tropomyosin inhibit actin and myosin interaction.
• T: binds troponin complex to tropomyosin.
• C: high affinity calcium binding sites, signalling contraction.
• The latter bond, drives TnI away from Actin, allowing its interaction with myosin.
Tropomyosin
• Elongated molecule, made of two helical peptide chains.
• It occupies each of the longitudinal grooves between the two actin strands.
• Regulates the interaction between the other three!
Actin
• Globular protein.
• Double-stranded macromolecular helix (G).
• Both form the F actin.
Myosin
• 2 heavy chains, also responsible for the dual heads.
• 4 light chains.
• The heads are perpendicular on the thick filament at rest, and bend towards the centre of the sarcomere during contraction (row.)
• heads are 43nm apart
• Alpha myosin and beta myosin.
Titin
giant protein, greater than 1 µm in length, that functions as a molecular spring that is responsible for the passive elasticity of muscle
Titin function
• provision of passive force
• stability of the myosin filaments
• stability of sarcomeres on the descending limb of the force–length relationship
Myosin properties
Hydrolyses ATP
interacts with actin
Actin properties
Activates myosin ATP
Interacts with myosin
Tropomyosin
Modulates actin-myosin filaments
Troponin C
Binds Ca2+
Troponin I
Inhibits actin-myosin interaction
Troponin T
Binds troponin complex to thin filament
A-band:
the region of the sarcomere occupied by the thick filaments.
I-band
occupied only by thin filaments that extend toward the centre of the sarcomere from the Z-lines. It also contains tropomyosin and the troponins.
Z lines
bisect each I-band.
sarcomere
the functional unit of the contractile apparatus,
• region between a pair of Z-lines
• contains two half I-bands and one A-band.
sarcoplasmic reticulum
membrane network that surrounds the contractile proteins,
• consists of the sarcotubular network at the centre of the sarcomere and the subsarcolemmal cisternae (which abut the T-tubules and the sarcolemma).
transverse tubular system (T-tubule)
lined by a membrane that is continuous with the sarcolemma, so that the lumen of the T-tubules carries the extracellular space toward the center of the myocardial cell.
All-or-none’ principal
always maximally contracts
The cardiac sarcomere must function near the upper limit of their maximal length (LMAX) = 2.2 um
Where does myocardium originate from
Mesenchyma
Excitation-contraction coupling
- begins when the action potential depolarizes the cell and ends when ionized calcium (Ca2+) that appears within the cytosol binds to the Ca2+ receptor of the contractile apparatus.
- Movement of Ca2+ into the cytosol is a passive (downhill) process mediated by Ca2+ channels.
- The heart relaxes when ion exchangers and pumps transport Ca2+ uphill, out of the cytosol.
What does a myocardial cell rely on for aerobic metabolism
Free fatty acids
intercalated disks
Adjacent cells are joined end to end at structures called intercalated disks, within which are desmosomes that hold the cells together and to which the myofibrils are attached. Also found within the intercalated disks are gap junctions similar to those found in single-unit smooth muscle.
Normal range for central venous pressure
-2 -> +12 cmH2O
Causes of elevated central venous pressure
Heart failure
Cardiogenic shock
Obstructive shock
High circulating volume
Positive end-expiratory pressure ventilation eg CPAP
Causes of low central venous pressure
Hypovolaemic shock
Distributive shock
Left ventricular ejection fraction
Predictor of left ventricular systolic function
(Stroke volume/ end diastolic volume) x100
Normal left ventricular ejection fraction
50-65%
Factors affecting systemic vascular resistance
Nitric oxide, cytokines
Autonomic innervation
Endothelins
Vasoconstrictor peptides
Bind to g-protein coupled receptors
Endothelin-1 is most potent
Secreted by vascular endothelium
High levels associated with heart and renal failure
Endothelial nitric oxide production
Nitric oxide formed via oxidation of nitrogen atoms contained with L-arginine by NO synthase
Endothelial nitric oxide mechanisms of action
Activation of guanylate cyclase
Increased intracellular cGMP
Downstream cellular processes
Endothelial nitric oxide functions
Vasodilation
Increased vascular permeability
(Increases local immune cell migration to site of infection but may lead to septic shock via reduced vascular resistance and low BP)
Flick method
Tissue oxygen delivery = pulmonary oxygen absorption + pulmonary artery oxygen before gas exchange
How is cardiac output measured non-invasively
ECG or Doppler ultrasound
Diastolic distensibility
the pressure required to fill the ventricle to the same diastolic volume.
Contractility (inotropic state)
the state of the heart which enables it to increase its contraction velocity, to achieve higher pressure, when contractility is increased (independent of load)
Arteries
• low resistance conduits
• Elastic
• Cushion systole
• Maintain blood flow to organs during diastole
Arterioles
• principal site of resistance to vascular flow
• TPR = total arteriolar resistance
• Determined by local, neural and hormonal factors
• Major role in determining arterial pressure and distributing flow to tissues/organs
• Vascular smooth muscle determines radius
• VSM contracts → decrease radius (vasoconstriction) → increases resistance → decrease flow
• VSM relaxes → increases radius (vasodilation) → decreases resistance → increase flow
• myogenic tone- VSM never completely relaxed
Capillaries
• 40000km and large area → slow flow
• Allows time for nutrient/waste exchange
• Plasma or interstitial fluid flow determines the distribution of ECF between these compartments
• Flow also determined by arteriolar resistance and number of open pre-capillary sphincters
Veins
• compliant
• Low resistance consists
• Capacitance vessels
• Up to 70% of blood volume but only 10mmHg
• Valves aid venous return against gravity
• Skeletal muscle/ respiratory pump aids return
• SNA mediated vasoconstriction maintains VR/VP
Lymphatics
• fluid/ protein excess filtered from capillaries
• Return of the interstitial fluid to CV system via thoracic duct and left subclavian vein
• Uni-directional flow aided by smooth muscle in lymphatic vessels; skeletal muscle pump; respiratory pump
Measuring BP using a sphygmomanometer
using brachial artery (convenient to compress and level of heart): sounds (Korotkoff)
0. > systolic pressure = no flow, no sounds
1. Systolic pressure = high velocity = tap
2-4. Between S and D = thus
5. Diastolic pressure = sounds disappear
Arterial Baroreceptors:
• short term regulation of bp (minute-minute control)
• New baseline formed of arterial pressure as deviated from the normal baseline for more than a few days
• Can lead to hypertension if new baseline is higher
Cardiopulmonary Baroreceptors:
• atria, ventricles and pulmonary artery
• When stimulated, decreased vasoconstrictor and decreased bp
• Decreased release of angiotensin, aldosterone and vasopressin leads to fluid loss
Chemoreceptors
• Chemosensitive regions in medulla
• high PaCO2 →vasoconstriction- high peripheral resistance and high blood pressure
• Low PaCO2 → low medullary tonic activity this low bp
• Similar changes with high and low pH
• PaO2 has less effect on medullar- moderate reduction in PaO2 = vasoconstriction / severe decrease = general depression
• Effects of PaO2 mainly regulated by peripheral PaO2
Short-term BP control
• Baroreceptors
• ↑BP ⇒ ↑Firing ⇒ ↑PNS/↓SNS ⇒ ↓CO/TPR = ↓BP
Long-term BP control
• Volume of blood
• Na+, H20, Renin-Angiotensin-Aldosterone and ADH
Peripheral bp control
• very sensitive to PO2 decrease as well as PCO2 increase and pH decrease
• Increased sympathetic outflow- results in increased TPR
• chemoreceptors involved in control of breathing
• Decreased PO2 decreases the parasympathetic output to the heart → increase heart rate →increase CO
Central bp control
• most sensitive to CO2 and pH
• Less so to O2
• Increased firing leads to sympathetic outflow
• Arterial vasoconstriction in skeletal muscle, renal and splanchnic system
• Increased TPR
Main neural influences on medulla:
• Baroreceptors
• Chemoreceptors
• Hypothalamus
• Cerebral cortex
• Skin
• Changes in blood [O2] and [CO2]
CV reflexes also require hypothalamus and pons
• Stimulation of anterior hypothalamus ↓ BP and HR;
• The reverse with posterolateral hypothalamus
• Hypothalamus also important in regulation of skin blood flow in response to temperature
• Cerebral cortex can affect blood flow & pressure.
• Stimulation usually ↑ vasoconstriction
• Emotion can ↑ vasodilatation and depressor responses eg. blushing, fainting. Effects mediated via medulla but some directly
Baroreceptors
• found in carotid sinus and aortic arch primarily
• Secondary found in veins, myocardium and pulmonary vessels
• Afferent- glossopharyngeal nerve to medulla
• Efferent- sympathetic and vagus X
• Firing range proportional to medulla
• Increased bp sensed by Baroreceptors which is then sent via the glossopharyngeal (IX) to the medulla where there is increased firing which results in stimulation of parasympathetic (X) nerve and decrease in sympathetic stimulation
• Results in decrease CO and TPR- BP = CO x TPR
Circulating hormonal factors:
Vasoconstrictors:
• epinephrine- acts on alpha receptors
• Angiotensin II
• vasopressin
Circulating hormonal factors
Vasodilators:
• epinephrine - acts on beta receptors
• Atrial natriuretic peptide (ANP)
Myogenic auto regulation of bp
• intrinsic ability of an organ
• Constant flow despite perfusion pressure changes
• Renal/cerebral/coronary = excellent
• Skeletal muscle/splanchnic = moderate
• Cutaneous = poor
• Brain and heart: intrinsic control dominates to maintain BF to vital organs
• Skin: BF is important in general vasoconstrictor response and also in responses to temperature (extrinsic) via hypothalamus
• Skeletal muscle: dual effects:
-at rest, vasoconstrictor (extrinsic) tone is dominant
-upon exercise, intrinsic mechanisms predominate
What governs flow:
- Ohm’s law- flow = pressure gradient / resistance
- Poiseuille’s equation- flow is inversely proportional Radius ^4
Main function of auto regulation
Mechanism that allows vascular resistance to be adjusted to maintain a constant blood flow in an organ across a pre-determined range of arterial pressures
Seen in the kidneys and brain (as constant perfusion is essential for the organs)
How long does the AVN delay the impulse for approximately
120 ms
How many cusps does the aortic valve have
3
Which 2 variables are linked by the Frank-starling mechanism
Stroke volume and preload
What changes would you expect to the left ventricle following positive inotropy and chronotropy as well as sympathetic stimulation
Increased systolic pressure, stroke volume, stroke work and heart rate
Decreased end-systolic and end-diastolic volume (as more blood ejected from the heart)
Which peptide produced by ventricular myocytes is tested for when suspected heart failure
B-type natriuretic peptide (BNP)
Hormone produced and secreted by ventricular cardiomyocytes when excessively stretched and so unable to pump blood as effectively
Elastic arteries
Largest and closest to heart
Elastin in media/externa——-> expand and recoil to absorb pressure
Muscular arteries
Thick muscular walls
Includes coronary arteries
When is the heart normally perfused
Diastole
What is flow to capillary determined by
Arteriolar resistance
Pre-capillary sphincters
Plasma/ISF flow
What maintains a pressure difference in the veins
Respiratory pump-diaphragm contraction
Average heart rate
72 bpm
60-100 bpm
Ejection fraction
Stroke volume/ end-diastolic volume = 65%
Blood flow equation
Blood flow = velocity x cross-sectional area of vessel
Systolic blood pressure range
100-150 mmHg
Diastolic blood pressure range
60-90 mmHg
Level of auto regulation
High: renal, cerebral, coronary
Moderate: skeletal, splanchnic
Poor: cutaneous
Local vasoconstrictors
Endothelin-1
Local vasodilators
NO, prostacyclin, bradykinin, adenosine, tissue factor
Central chemoreceptors in medulla detect high H+ because of…
CO2 + H2O ——> H2CO2 ——> H(CO3)- + H+
How long does the cardiac cycle plateau last for
200ms
Left sided heart failure
Less blood pumped by left ventricle ——> blood backs up in pulmonary circulation ——> increases pulmonary pressure ——> pulmonary oedema——> breathless
Right sided heart failure
- Respiratory failure or left side heart failure ——> increases pulmonary pressure (hypertension)
- Harder for right ventricle to pump into pulmonary artery
- Systolic dysfunction——> RV hypertrophy
- Decreases filling ——> diastolic dysfunction
- Blood backs up in systemic circulation
- Increases central venous pressure ——> peripheral oedema and ascites (abdomen)
Elasticity
Myocardial ability to recover its normal shape after removal of systolic stress
Compliance
Relationship between change in stress and resultant strain: EDP - EDV relationship
Contractility/ inotropic state
Heart can increase its contraction velocity to increase pressure : ESP - ESV relationship
Diastolic distensibility
Pressure required to fill ventricles to same diastolic volume
Leaky mitral/ bicuspid valve
Blood goes back into atrium ——> preload has normal filling plus what went back into atrium
This increases preload ——> ventricle needs increased pressure to overcome resistance ——> hypertrophy
Length of ventricular systole
0.3s
Ventricular contraction
Pressure in V>A —> AV valves shut (R peak)
Isovolumic contraction: SL valves remain shut- increase in pressure but same volume
QRS complex: ventricular depolarisation
Ventricular ejection
Pressure in V> aortic or pulmonary —> SL valves open
As 70% of blood is ejected:
Decreases ventricular pressure and ejection force
Atrial filling starts
Leaves 30% of blood (EDV)
ST interval
Ventricular diastole time
0.5s
Ventricular diastole
Isovolumic relaxation: pressure in V (<80mmHg) < aorta so SL valves shut- T wave ends
Passive blood flow when AV valves open (85-95% of blood)
Rapid filling: pressure in A>V
Slow filling (diastasis): pressure in A=V
Just after P wave —> atrial booster- contraction (5-15% blood) - PR interval ATRIAL SYSTOLE
Percentage of blood moved in passive blood flow from atria to ventricle
85-95%
Neuromuscular junction
- Nerve impulse reaches NMJ —> Ca2+ release triggers ACh exocytosis (all NMJs are excitatory) —> ACh binds to post synaptic receptor on motor end plate —> Na+ entry into sarcoplasm
Produces wave of depolarisation
What is force of contraction proportional to
Concentration of cytosolic Ca2+
Nitric oxide production:
• ACh and insulin stimulate calcium release which leads to L-arginine being converted to NO aided by NO synthase
Endothelin-1 production:
• angiotensin II, vasopressin, cytokines, thrombin, oxidative reactive species, shearing forces all stimulate endothelin-1 production
• Big endothelin-1 converted to endothelium-1 by endothelium converting enzyme
• Endothelin-1 acts on G coupled proteins which stimulate IP3 and calcium release, resulting in smooth muscle contraction
Troponin blood test
Dead cardiac muscle- releases troponin- sign of myocardial infarction
Renin-angiotensin-aldosterone system
acts to increase blood volume and systemic vascular resistance. Renin (released from granular cells in the juxtaglomerular apparatus of the kidney) converts angiotensinogen (protein from the liver) into angiotensinogen 1. ACE then converts it into angiotensin 2- which causes vasoconstriction in systemic circulation and renal microvasculature (constricting the efferent arteriole). ACE also removes bradykinin (a vasodilator) causing further vasoconstriction. Angiotensin 2 increases salt absorption in the kidney through activation of aldosterone, leading to an increase in plasma volume and blood pressure
Frank-starling law and heart disease
• The muscle contraction of the heart may weaken due to overloading of the ventricle with blood during diastole. In a healthy individual, an overloading of blood in the ventricle triggers an increases in muscle contraction, to raise the cardiac output. In heart failure, however, this mechanism fails due to weakened cardiac muscles which results in a failure of the heart to pump an adequate amount of blood.
• To compensate for the lowered cardiac output, the heart rate rises. This makes the condition worse as the heart muscles require more nutrients to work and the myocardial muscles pump at an increased rate.
• Stroke volume reduces as the systole or diastole contractions start to fail. If the volume of blood in the ventricle at the end of systole rises, it means less blood is ejected. If the volume at the end of diastole is decreased, it means less blood is entering the heart during diastole.
Diastolic impairment
lack of relaxation of atria so less passive flow of blood from atria to ventricle
Myocardium normally perfused:
Because these vessels traverse the myocardium, myocardial contraction during systole compresses arterial branches and prevents perfusion. Therefore, coronary perfusion occurs during diastole rather than systole.
Occlusion of the LAD:
• can lead to an often-fatal heart attack know was a widowmaker
• LAD artery is the most commonly occluded of the coronary arteries. It provides the major blood supply to the interventricular septum, and thus bundle branches of the conducting system. Hence, blockage of this artery due to coronary artery disease can lead to impairment or death (infarction) of the conducting system. The result is a “block” of impulse conduction between the atria and the ventricles known as “right/left bundle branch block.”
• Right bundle branch block: left ventricle contracts first → signal carried to right side via Purkinje fibres → right ventricle contracts
• Left bundle branch block: right ventricle contacts → left ventricle contracts
• Generally results in ST segment elevation in precordial leads and reciprocal ST segment depression in inferior leads
• Can cause stable or unstable angina
Occlusion of the right coronary artery:
• may cause infarction of the inferior wall of the left ventricle with or without right ventricular (RV) myocardial infarction (MI), manifested as ST-segment elevations in leads II, III, and aVF.
• right coronary artery branches supply the sinus and atrioventricular nodes; hence, blockage in these vessels can lead to conduction abnormalities
• causes heart rate to slow until it stops
Symptoms of heart failure
Fatigue
Weakness
Shortness of Breath on exertion
Shortness of Breath at Rest
Cough and wheezing
Anorexia / loss of appetite
Paroxymal nocturnal dyspnea
Nausea
Abdominal pain
Nocturia
Signs of heart failure
Pulmonary edema
Pleural effusion
Tachycardia
Narrow pulse pressure
Cardiomegaly
Peripheral edema
Jugular vein distension
Earliest structurally apparent lesion in atherosclerosis
Fatty streak formation as the result of foam cell accumulation in the vessel wall
First step in atherosclerosis
Endothelial cell injury
Mean systemic filling pressure
The pressure that would be present in the circulation if the heart was removed and the system was allowed to equilibrate
What variables are on the x and y-axis of frank-starling mechanism
X-axis = end-diastolic volume
Y-axis = stroke volume
Ions responsible for increasing contractile force of cardiomyocytes
Intracellular Ca2+
Convulsions, excessive muscle contractions, ECG shows irregular arrhythmias. Blood test would show abnormal result for
Hypocalcaemia- causes increased nervous system excitement by lowering threshold for depolarisation as less Ca2+ to block sodium channels and inhibit depolarising
What does the dicrotic notch correspond to
Closure of the aortic valve
What is the inflow phase composed of
Diastole (blood enters ventricles from atria passively) and atrial systole
What is the main site for the production of BNP
Cardiomyocytes in the ventricles
When is pro-BNP produced by ventricular cardiomyocytes
In response to stretch caused by increased blood flow in the vernricles
BNP and pro-BNP and heart failure
High levels in heart failure as a result of stress on the ventricles
What causes the first heart sound
An increase in ventricular pressure and a decrease in atrial pressure causing the AV valve to close
What effect would chronic anaemia secondary to menorrhagia have on the oxygen dissociation curve
Rightward shift of the curve
Role of 2,3-bisphosphoglycerate in the oxygen dissociation curve
Causes curve to shift to the right- decreases haemoglobin’s affinity for oxygen to encourage unloading of oxygen at respiring tissues
The haldane effect
Oxygen binding to Hb causes a decreased affinity of Hb for CO2
In what way does the heart try to compensate for loss of function during heart failure
Elevated right atrial pressure
- partially offsets decline in cardiac output by increasing preload = frank-starling law
Normal ejection fraction
50-55%
What is the main determinant of diastolic blood pressure
Total peripheral resistance
Which ion channels are open during the plateau phase of cardiac action potential
Calcium and potassium
What mediator promotes coronary vasodilation
Adenosine - acts on A2 receptors of smooth muscle cells
How would anaemia affect the peripheral chemoreceptors in the body
No activation of peripheral chemoreceptors in carotid bodies as respond to dissolved oxygen but oxygen bound to Hb
Blood flow =
Change in pressure/resistance
Which type of blood vessels primarily control blood flow through the capillaries
Arterio-venous anastomoses
In heart failure excitation-contraction coupling is deranged as a result of which process
Up regulation of the sarcolemmal Na+/Ca2+ exchanger resulting in increased efflux of Ca2+ from the cardiomyocyte
The transient increase in Ca2+ concentration is reduced so the contraction is weaker
During the Valsalva manoeuvre what happens to venous return
Decreases due to compression of thoracic veins
Blockage to LAD
Impaired conductivity
Blockage of RCA
Inferior myocardial infarction
What causes the dicrotic notch
Increase in aortic pressure upon valve closure- blood rebounds against valve
What can severe pulmonary hypertension cause
Right side heart failure - right ventricle must pump blood harder through pulmonary artery
What is pulmonary oedema in the presence of a normal central venous pressure a sign of
Left heart failure - blood backs up pulmonary system, increasing hydrostatic pressure
What is raised central venous pressure a sign of
Right side heart failure
Which coronary artery if blocked is most likely to result in a fatal heart attack
Left main coronary artery
Carotid sinus massage is a bedside procedure used to investigate unexplained dizziness, falls or faints.Which of the following effects may be caused by stimulation of the carotid sinus?
Reduced blood pressure
Blood pressure control is complex and adapts to the changing needs of the body. Which statement about the physiology of blood pressure control is correct?
Local nitric oxide release overrides central control
What percentage of cardiac output goes to the brain
15%
What percentage of cardiac output goes to the skin
5%
What percentage of cardiac output goes to the heart
5%
What percentage of cardiac output goes to the muscles
20%
What percentage of cardiac output goes to the kidneys
20%
What percentage of cardiac output goes to the liver
25%
What percentage of cardiac output goes to the other organs
10%
