Cardiovascular Flashcards
What are the divisions of the mediastinum?
Superior mediastinum- above the angle of louis
Inferior mediastinum- below the angle of louis
Anterior mediastinum: Anterior to the heart. Includes the thymus in children
Middle mediastinum: The heart
Posterior mediastinum: posterior to the pulmonary trunk
What is the surface anatomy of the chest?
Parasternal- either side of the sternum (RA is parasternal)
Midclavicular- Apex of the heart is in 5th intercostal space in the midglavicular line
Midaxillary- in the plane of the armpit
Where would you insert a needle to drain the heart/pericardium?
Up under the xiphi process
What are the layers of the pericardium?
Fibrous pericardium- very stiff and adherent to the diaphragm
This is fused with the serous pericardium, and both are innervated by the phrenic nerve
The serous pericardium is made up of the parietal pericardium. Between the visceral and parietal pericaria is the pericardial cavity, which can fill with puss, blood, fluid and air, especially due to trauma.
The visceral pericardium is made of the epicardium, myocardium and endocardium.
What are the main sinuses of the heart itself?
The oblique pericardial sinus, which is formed by reflection onto the pulmonary veins of the heart. In addition, the transverse pericardial sinus separates the arteries and veins, and runs between the two. This is a good place to clamp the arteries and put the heart on bypass
What are the grooves of the heart?
AV groove/coronary sulcus separates the RA from RV, and the right coronary artery runs within it.
The anterior interventricular groove runs between the ventricles, and contains the left anterior descending (LAD) artery
Posteriorly, the coronary sinus runs between atria and ventricles, holding a big vein which draws blood from the whole heart and deposits it in the right atrium
What do the components of the heart look like on xray?
It kind of looks like a sorting hat, with the diaphragm as the brim. The right atrium is on the right, RV/Diaphragm at the base, left ventricle topped by the left auricle. Above the left auricle are two small bumps; the pulmonary trunk and the arch of the aorta.
What is the arterial supply of the heart itself?
From the aorta, the right coronary artery runs between the RA and RV, before branching into the right marginal branch and posterior branches, before giving off the AV nodal branch and the posterior/descending interventricular branch.
The Sino-atrial nodal branch runs to the SA node.
The left circumflex artery and the LAD run down and supply the left ventricle.
Where do the anastomoses of coronary circulation occur?
- Between the left circumflex artery and posterior branches of the right coronary artery
- Between the posterior/descending interventricular branch and the LAD
What is the venous drainage of the heart?
Coronary sinus lies posterior to the left atrium in the AV groove, and dumps into the RA.
What are the structures found within the right and left atria and ventricles?
RA: smooth venous atrium with ridged part containing musculi pectinati, which contract in diastole. A ridge called the crista terminalis separates them. Foramen Ovale separates the right and left atria
RV: Papillary muscles found in the ventricle wall attach to chordae tendineae. The septomarginal trabecula is a muscular tissue running from interventricular septa to the ventricular wall, helping to make an electrical shortcut
LA: Completely smooth, with ridges found only in hte auricle, which is also the only contractile part.
LV: Same as RV, but the wall is 3x thicker
What are the different valves within the heart? What are their structures?
Pulmonary/Aortic valve: Three pockets which fill with blood due to backflow after systole ends. The pressure of each pocket pushes against one another to keep the valve shut
Tricuspid/bicuspid valve: During ventricular systole, the papillary muscles contract and pull the flaps downward to act against regurgitation
Where can heart valve sounds best be heard?
Pulmonary valve: 2nd intercostal space in left parasternal plane
Aortic valve: 2nd intercostal space in right parasternal plane
Bicuspid valve: Apex of the heart- 5th intercostal space at midclavicular plane
Tricuspid valve: 5th intercostal space in left parasternal plane
What is the progression of electrical activity through the heart?
SA node –> Atrioventricular node –> Bundle of His (AV bundle) –> Right and left bundle branches–> Septomarginal trabecula –> purkinje fibres to walls of ventricles
What can happen due to coronary artery failure?
- R coronary artery: SA and AV branches fail, so result is a rhythm disturbance
L coronary artery: RV and LV no longer innervated- pump failure
What are the preliminary changes in the heart as an AP is conducted?
- Ventricles stiffen and papillary muscles contract. Septum stiffens. This is all before ventricular contraction
How is the heart innervated?
The pericardium is innervated by the phrenic nerve. The superficial and deep cardiac plexuses innervate autonomically, with vagus responsible for parasympathetic stimulation. As the innervation of the heart itself is autonomic, damage to these nerves leads to a vague crushing pain when irritated
What is the difference between a stenotic and regurgitating heart?
- Stenotic doesn’t flow well due to increased wall thickness
- Regurgitating flows in the wrong directions and is heard in diastole for the upper valves, or systole for the lower valves.
What are the four highest risk factors for CVD?
- A high saturated fat diet- this is a must- have factor for CVD
- Smoking
- High BP
- Diabetes
The last three are also stroke risk factors
What are the three main properties exhibited by the cardiac myocytes?
- Exitability
- Conductivity
- Automaticity
What are the two types of action potentials seen within cardiac muscle?
Cells with a fast response
Cells with a slow response
What are the phases of an action potential in cells with a fast response?
Resting potential is -90mV
Threshold potential is -70mV in ventricles (or -30- -60mV in atria)
Phase 0: Rapid depolarisation due to rapid increase in sodium permeability. Fast inward Na due to electrical and concentration gradients
Phase 1: Early repolarisation to near 0mV due to transient outward potassium current
Phase 2: Plateau- Na channels inactivate and the cell becomes refractory. The inward slow Ca (L-type and CICR), as well as the outward potassium current, are almost equal but slowly decreasing
Phase 3: Repolarization: Outward potassium currents switched on after a delay due to delayed rectifier channel. Other potassium channels also activate- iKATP due to decreased ATP, or iKAch due to increased ACh
Phase 4: Resting, with a high potassium conductance
What are the background movements of ions occurring in an action potential?
Ca pump removes Ca
Na/Ca exchanger takes 3Na+ in for 1 Ca2+ out, helping to depolarize
Na+/K ATPase exchanges 3Na+ for 2 K+, causing repolarization
What is the action potential of cells with a slow response?
They have an unsteady resting membrane potential, which is higher than usual. They may be pacemakers or non pacemaker cells, and are categorized by their slow Ca2+ driven current (rather than Na+ driven)
What is a refractory period, and what are the potential phases involved with this time?
Absolute refractory period- when the membrane can’t be re-excited
Relative refractory period- larger than normal stimulus needed for AP generation- although impaired conduction
Supernormal period- get propagated AP from weaker than normal stimulus, although impaired conduction
Full recovery time- may extend beyond return to Resting dependence
The longer than normal refractory phase prevents tetanus of the heart
What is the interval-duration relationship?
The duration of the AP is partly determined by the preceding diastolic interval- faster HR means a shorter AP
How are cardiac myocytes conductive?
They respond due to electrical stimulation, thanks to its spread throughout the myocardium due to electrical coupling due to nexus junctions between neighbouring cells
Their structure is laminar- not uniformly continuous, but continuous enough to propogate action potentials
What is automaticity in cardiac myocytes?
Refers to the ability of cells to initiate an electrical impulse due to their own pacemaker activity. Found in SA, AV and his-purkinje network
- Due to outward K and inward If (Na)- activated at negative potentials- and ICa
What are some mechanisms for altering the rate of pacemaker discharge?
- Alter slope- change rates of inwards/outwards currents
- Alter threshold potential
- Alter max diastolic pressure- how far down the repolarization curve reaches
What are the hormones released by the PNS and SNS to regulate HR?
PNS- releases ACh to slow HR
SNS- releases noradrenaline to increase HR
What are the speeds of the various components of the cardiac electrical sequence?
AV node is slow, to allow atria to top up the ventricles before initiating contraction. Atria and ventricles are insulated from one another by the fibrous skeleton
Bundle branches and purkinje fibres are fast
What should we note about conduction within the heart?
- SA node is normally the pacemaker due to its high intrinsic rate, and overdrive suppression of other pacemakers due to hyperpolarization
- AV delay may be subject to blockage
- Purkinje network is rapid to activate the whole endocardium synchronously
- Velocity is proportional to the square root of the radius of the fibres
- Velocity depends on the rate and amplitude of depolarization
What is wolff-parkinson-white syndrome?
An abnormal structure between the atrium and the ventricles, which allows the bypass of the AV node. It leads to re-entrant arhythmia (short interval between contractions, due to charge propagating a continuous loop between atria and ventricles.
What are the features, function and mean pressure of the left ventricle?
- Thick muscular walls, inlet and outlet valves
- Pump
- 95mmHg pressure
What are the features, function and mean pressure of the large/medium arteries?
- Muscular walls for control, C. T. for strength
- Conduct and store large volumes of blood/distribution and tone
- 85-95mmHg
What are the features, function and mean pressure of the arterioles, metarterioles, and precapillary sphincters?
- Smooth muscle to control diameter, little CT
- Control flow to capillaries based on demand
- 35-85mmHg
What are the features, function and mean pressure of the capillaries?
- Endothelium, no muscle or CT
- Exchange
- 15-35mmHg
What are the features, function and mean pressure of the venules?
Thin walled, large diameter
- Collect blood
- 0-15mmHg
What are the features, function and mean pressure of the veins?
- Think walled, variable structure and valves
- Conduct and store blood
- low
What are the features, function and mean pressure of the R atrium?
- Thin muscular walls
- Reservoir for blood
- 0-2mmHg
What are the three tunics comprised of in elastic arteries?
- Intima: endothelium with internal elastic lamina separating
- Media: A lamellar unit alternating between smooth muscle, collagen and elastin
Fenustrated elastin layers
Adventitia: Vasa vasorum supply the layer, with collagen and elastin fibres
What are the three tunics comprised of in muscular arteries?
Intima: Endothelium with internal elastic lamina
Media: Collagent and elastin fibres, but not nearly as many or as large. External elastic lamina
Adventitia: Vasa vasorum, collagen and elastin fibres with nerves
What are some common arterial diseases?
- Atherosclerosis: Endothelium damaged, causing increased intima thickness and accumulation of macrophages. It is most often caused by high cholesteol, and the free fat cells are digested by the macrophages, forming foam cells. The IEL breaks down, and blood clots can form and occlude
- Aneurysm: Dissecting mainly found in thoracic and abdominal aorta, where the weakened intima causes blood to pool in the media Berry found in brain branch points, around circles of willis. These form large pods that can burst
- Hypertension: 140/90+. Intima thickens, media thickens to maintain pressure, and IEL may duplicate. Increased by obesity, stress, salt and smoking
What are the three tunics comprised of in arterioles?
Endothelium and then IEL, with 2-3 layers of smooth muscle before a surrounding of collagen. Has a wall thickness equal to lumen diameter.
What structures are located at the trans-thoracic plane (angle of louis)?
- Arch of the aorta
- Arch of azygous vein
- Trachea (may be bifurcated)
- Thoracic duct (crosses behind oesophagus from RHS to LHS
- Cardiac plexus
- Ligamentum arteriosum
- Good place for jugular venous pressure
What are the great veins of the thorax, from external to internal?
External jugular (not great vein) empties into subclavian, which then combines with the internal jugular to form the brachiocephalic vein. The two combine to form the SVC. The left brachiocephalic vein is longer due to it needing to cross the midline
What are the great arteries of the thorax?
Aortal branches into brachiocephalic trunk, and then into common carotid and subclavian (same on each side.
Where do the phrenic and vagus nerves run in the thorax?
- Phrenic: from C345 down the LHS and RHS of the pericardium
Vagus: From CX. Right slides under subclavian artery to give off the R recurrent laryngeal nerve, while L goes under arch of aorta to give off L recurent laryngeal. They then wrap around the oesophagus to give the ant (left) and post (right) vagal plexuses
What is the significance of the branch points of the recurrent laryngeal nerves?
These control the voice- any change can be due not just to throat conditions, but also to bronchial tumor, and aortic aneurysm etc.
Why would it be necessary to insert a central venous line?
Deliver blood/fluids immediately
Deliver toxic drugs without destroying the weaker peripheral veins
Measure pressures in heart chambers
What are the 4 main veins that can have a central line?
- External Jugular
- Femoral
- Internal Jugular
- Subclavian
What are the pros and cons of putting a central line in the external jugular?
Pros
- Easy to access and superficial
- Less likely to cause a pneumothorax
Cons
- Small, difficult vein to threat (insert a tube)
- Uncomfortable for the patient as it sits below their ear
What are the pros and cons of putting a central line in the femoral?
Pros - Easy to access, especially during CPR - No chance of pneumothorax Cons - Increased infection risk - Increased clot risk - Reduction in mobility
What are the pros and cons of putting a central line in the internal jugular?
Pros - Easy to find and threat Cons - Can be uncomfortable - Risk carotic artery- supplies the brain and can form a clot or an air embolism, resulting in stroke - Risk of Pneumothorax - Impossible during CPR
What are the pros and cons of putting a central line in the subclavian vein? (Most common)
Pros
- Most common long term
- Comfortable
- Less likely to be dislodged during CPR and intubation
Cons
- Risk pneumothorax/subclavian airway puncture
- Impossible to apply pressure if artery punctured, as below clavicle
- Risk to brachial plexus.
What do EKG leads record (as a general statement)?
Record potential difference in different sites of the body due to electrical activity in the heart- the body is able to act as a conductor
What are the main components of an EKG and what do they represent?
P wave: atrial depolarization, small mass and hight, slow reflecting time taken- even though it has a similar timespan to ventricles, it has a smaller mass
PR segment: Between P and start of QRS. Atria depolarized, isoelectric. Reflects time in AV node, bundle and bundle branches.
QRS Complex: Ventricular depolarization- greater magnitude than P due to more mass, shorter than P wave relative to mass. Also includes atrial repolarization (though not visible)
PR interval: Total time for wave to run from atria to ventricles
ST segment- Isoelectric spot, when there is no moving wavefront. Plateau of AP in ventricles
T wave: Asynchronous repolarization of ventricles, as the cells have slightly differing peak times
QT interval: Reflection of ventricular action potential duration
How does the EKG use vectors to represent charge?
When a wavefront moves within the heart, it causes a reversal of charge in the surrounding extracellular tisse. This forms a dipole, with a positive and a negative charge side by side, and moving in the direction of flow. This is represented by a vector (which is plotted on the ECG). The orientation represents the direction the dipole is travelling (relative to the ECG line), while the length represents strength.
What factors affect measured potential of a dipole?
- Magnitude of the change
- Orientation of the dipole and the electrodes
- Distance between the dipole and electrodes- potential difference is higher close in and vice versa.
What is represented on each point of the QRS complex?
- Q = ventricular septal depolarization
- R = ventricular apex depolarizing
- S = ventricular base depolarizing
What can be inferred from the orientation of the T wave?
As the ventricular depolarization runs from endocardium to epicardium, and repolarization is vice versa, we know that the AP duration of the endothelial cells is longer than those in the epicardium
What are some potential issues with an EKG?
- Assumes body is a volume conductor regardless of tissue type
- A single dipole is not a good representation of a wavefront
What is a bipolar EKG?
Measures a single vector between two points. This is used in Einthoven's triangle, where leads are set on the Right arm, left arm and leg in order to string leads together in a triangle. The differences between each two-point interval can then be calculated. Lead 1 = LA-RA Lead 2 = LL - RA Lead 3 = LL - LA Therefore: I + III = II
What is a unipolar EKG?
Uses the potential of a single electrode relative to a point of reference- usually compared to zero, called the indifferent electrodes. This means that when the dipole faces the exploring electrode it is recorded as positive.
It also allows crosses across the original einthoven’s triangle, representing 6 leads (augmented unipolar leads)
What is a 12-lead EKG?
An additional 6 leads are added to the augmented unipolar limb leads, allowing the coronal and horizontal planes to be recorded.
What features of an EKG are important?
= Rate = Rhythm - P waves - PR interval - QRS complex - ST segment - T waves
What are the structures held within the posterior mediastinum?
Azygous veins Thoracic Duct Oesophagus Thoracic Aorta Nerves
How do the azygous veins work?
They link the superior and inferior vena cavae. The RHS (azygous vein) receives systemic as well as RHS intercostal blood and drains into the SVC
The accessory hemiazygous (sup) and hemiazygous (inf) veins run on the left side, draining the superior and inferior intercostals, respectively.
What is the thoracic duct and how does it work?
It’s a large lymphatic duct running from the abdomen. It starts at the cisterna chyli, and runs anterior to the vertebrae up the midline It crosses from being more RHS to more LHS at the thoracic plane. It drains into the point where the left internal jugular and subclavian veins meet.
It can get blocked at this point.
It is important to check its associated nodes, as the whole body (apart from the R arm and face) drain their lymph through here
Where does the oesophagus run and how is it suppled? What can go wrong with it?
- It runs behind the left main bronchus and arch of the aorta
- It can be constricted by the diaphragm, as well as by a large aneurism in the aorta, or a lung tumor.
Upper 2/3: Supplied by branches of the thoracic aorta, azygous vein and sympathetic trunks
Lower 1/3: Supplied by left gastric artery, gastric veins (to portal system) and vagus nerve
What are the nerves within the posterior mediastinum?
- Sympathetic trunks
- Phrenic nerves
- Vagus nerves
What can portal hypertension result in and why?
There are no valves to prevent backflow in the visceral veins so:
- Caput medusae
- Anal varices
- Oesophageal varices
What is coarctation of the aorta and how does the body adjust to this?
Narrowing of the aortic arch (a birth defect). Usually after the main 3 branches have been given off
Body supplies descending aorta as bloodflow reverses through the post. intercostals- supplied by both sides of anterior intercostals instead
What are signs of aortic coarctation?
- Radial pulses and femoral pulses being out of sync between each other and the sides of the body.
- Notching of the ribs on the chest X ray due to the size of the artery causing them to wear away (more pressure in other arteries)
What does Wolf Parkinson White syndrome look like on an EKG?
It shows up as a shortened P R interval due to early conduction from atria to ventricles
Also a wide QRS complex as while the conduction starts early, the conduction pathway isn’t incredibly fast.
Additionally, there is a delta wave between Q and R as conduction isn’t as fast as usual within the ventricles
What are the symptoms of WPW syndrome and how is it normally treated?
May be asymptomatic- although can have unexplained syncope or palpitations.
Drugs control fast rhythms, or surgery can correct the false pathway
What is LQTS, how does it present and how is it treated?
Long QT syndrome- an abnormally long delay between ventricular de- and re-polarization.
Can be drug induced (from arrhythmia drugs) or genetic (due to ion channel mutation)
Most commonly K+ delayed rectifier channel. Causes differences in refractoriness of myocytes and abnormal ventricular activation (possibly followed by arrhythmia and fibrillation) Assoc. with syncope and sudden death
Treated with arrhythmia prevention and termination
How can EKGs diagnose conduction disturbance, heart/lung structure and electrolyte disturbance?
- AV/bundle branch blocks- will see long PR intervels
- Heart and lung structure- will see large deflections on the EKG
- Potassium disturbance: Hyperkalemia leads to faster repolarization and high peaked T waves. Hypokalemia opposite
What features are seen in an EKG for each type of ischaemic heart disease?
- Ischaemia: T wave affected
- Injury- ST segment
- Infarction- QRS complex
What is the sequence of changes in a Q wave due to infarction?
- Tall peaked T waves over leads facing damaged area
- ST segment elevation (hours later)
- reduced R wave amplitude
- T wave inversion (days later)
- Pathological Q waves (usually only residual signs of MI)
- ST segment returns to normal (days later)
- T waves return to normal (weeks)
Reciprocal changes may be seen in leads facing opposite the infarction
What T wave changes are seen in myocardial infarction?
Not specific to MI- but earliest signs of acute MI. Lasts 5-30 mins after onset. Same mechanism as hyperkalaemia due to K+ leakage from damaged myocytes
What ST interval changes are seen in myocardial infarction?
ST Segment elevation- though mechanism depends on current of injury.
Systolic injury current: Ischaemic zone incompletely depolarized, so AP is different between two areas- the net current between leads is not 0 during this time
Diastolic injury current: Ischaemic zone is less repolarized than healthy zone so resting RMP is higher- so the ST elevation is also at this level.
What QRS changes are seen in myocardial infarction?
- Results in electrically inactive tissue forming a ‘window’ through which activity is reduced or absent (or, in opposite electrodes, amplified).
This results in reduced R wave height and QS complexes (no R wave)
What are some complications with EKG diagnosis of MI?
Changes are variable and sometimes absent
- Abnormal activation distorts EKG
- 12 lead EKG can’t show basal/pst. RV walls well
What is atherosclerosis? How is it different to arteriosclerosis?
- Atherosclerosis affects medium and large arteries, appearing as focal plaque thickenings. Arteriosclerosis is a general term for arterial hardening
What are the normal functions of endothelial cells in blood vessel walls?
Contains blood, selective transport into tissues, clotting and blood pressure control.
What are positive risk factors for atherosclerosis (increase risk)
Hyperlipidaemia
Cigarette smoking
Hypertension
Diabetes mellitus
Advanced age- lesions can be seen in all ages, but only present when progressed
Metabolic syndrome- fat stored in unsuited organs, increased insulin resistance, altered inflammatory predispositions
What are negative risk factors for atherosclerosis (decreased risk)?
High levels of HDL fats (transport saturated fats away from vessel walls)
Moderate alcohol consumption
Cardiovascular fitness
What is the pathogenesis of atherosclerosis?
- endothelial cell injury- caused by haemodynamic force of blood (high BP), chemical insults (smoking, lipids) or cytokines
Leads to altered permeability (and lipid infiltration), leukocyte adhesion and thrombosis activation
2, Chronic inflammation- leukocytes migrate into plaque
- Neutrophils arrive early, then monocytes enter and take up oxidised lipoproteins, forming foam cells. When these die they release their contents, promoting necrosis, cholesterol crystals/clefts, and calcification.
- Mast cells promote leukocyte & smth muscle movement into plaque, and degrade HDL
- Smooth muscle cells activated by macrophages, platelets and endothelial cells. Migrate to TI, producing cytokines and attracting leukocytes.
- Lipoproteins become oxidised, attracting monocytes and stimulating cytokines
What are the two anatomical components of a plaque?
Fibrous cap- with smooth muscle, macrophages, foam cells, fibres- fibroblasts secrete fibres to stabilize the atheroma
Necrotic center- cell debris, cholesterol crystals, foam cells, calcium
What can result from atherosclerosis?
- Often silent until sudden symtoms.
Once the plaque has grown, it can cause aneurysm and rupture due to wall weakening, occlusion by a thrombus due to plaque rupture/erosion/haemorrhage/mural thrombosis, or critical stenosis by progressive plaque growth
This commonly results in myocardial infarction, peripheral vascular disease, and CVD
What makes a plaque go from preclinical to clinical?
Entry into the vulnerable phase- thin/no fibrous cap, high lipid content and widespread inflammation
What are general features of the cardiac myocyte?
- Myogenic
- Striated
- Electrically coupled using nexus junctions
- Oxidative in metabolism
- Action potentials trigger CICR
How is the sarcolemma important in cardiac myocytes?
Forms the permeability barrier between intra- and extra-cellular contents. Continuous with the T tubules. Outer surface known as glycocaly
What are T tubules and why are they important in cardiac myocytes?
- Invaginations of the sarcolemma, rich in L type Ca2+ channels (DHPRs)
What is special about the intercalated disks of cardiac myocytes?
- They have 3 differentiations in their connection between cells:
- Nexus junctions
- Fascia adherens junctions
- Desmosomes (macula adherens)
What is the Sarcoplasmic reticulum and why is it important in cardiac myocytes?
- It’s an intracellular, Ca2+ storing membrane bound structure.
It includes junctional couplings with T tubules and with external sarcolemma.
Induces calcium induced calcium release due to RyR receptors opening and releasing Ca2+ when stimulated by Ca2+
Re-takes Ca2+ due to SERCA channels.
Also rich in calsequestrin, which buffers Ca2+ and helps return it to the SR by binding to Ca2+ and reducing the gradient for the pump to work again
What forms the space surrounding cardiac myocytes?
- Mostly vascular
- Some ground substance
- Few connective tissue and empty space
- A little collagen
What are the steps of contraction in a cardiac myocyte?
- AP spreads across the SL and T tubules
- Voltage causes DHPRs to open
- Influx of Ca2+ causes RyRs to open and release even more Ca2+
- Ca2+ binds TnC and allows crossbridges and contraction
- Additionally, Ca2+ is sensed by the mitochondria, and stimulates it to produce ATP
What is excitation contraction coupling?
Process by which electrical changes at surface membrane lead to changes in intracellular Ca2+ levels, which in turn causes contraction
What are DHPRs?
They are channels which are activated by voltage >-40mV and catecholamines to carry Ca2+ into the cell, contributing to the plateau
They trigger EC coupling, and are inhibited by the trigger of CICR, as well as by dihydropyridines, Mg2+ and low plasma Ca2+ content
What is microscopic SR release?
Occurs when Ca2+ leaks from the SR, making the whole cell Ca2+ transient. The amplitude and duration of these Ca2+ ‘sparks’ determines the body’s response to this (ie contraction or not)
How is Ca2+ able to be removed from the myoplasm? Why is this important?
- A low capacity, high affinity pump may be used- Ca2+ ATPase. This only contributes a little
- An ATP independent pump driven by the steep Na+ concentration across the sarcolemma. Although this operates in both directions- stimulated by low intracellular Na+ as well as high intracellular Ca2+ and negative membrane potential. This is also maintained by the 3Na+/2K+ pump.
Na+ also has spots of hot and cold concentration along the SR, driving its movement
Important as Ca2+ in via DHPRs must be removed to maintain balance
pH is also kept in balance by Na+/H+ exchangers - Majority is simply returned to the SR by SERCA transporters
What are the components of the microcirculation, and how does it control blood flow?
Arterioles (2-3 smth muscle) lead to terminal arterioles (1 layer smth muscle) lead to metarteriole (incomplete smth muscle) and into capillaries. These are opened/closed by precapillary sphincters so when the body is hot/parasymp these are open and allow the capillary network to become more perfused.
If wanting to direct the blood straight past the capillary bed, a thoroughfare channel connecting arterioles with venules is used.
Another type of channel can have no capillaries arising from it, termed Arteriovenous anastomoses. This can allow AV shunting. If it is closed however, it forces blood through the capillaries
What are the different classes of capillary and their features?
Continuous capillaries: May have closed intercellular clefts (tight junctions form a complete seal- eg. BBB) or open intercellular clefts (eg. muscle, lungs. Allows H2O, ions, other small molecules, but not plasma proteins)
Fenestrated capillaries: May have closed perforations (like glycocalyx, eg. in intestine) or open perforations (as in glomeruli)
Sinusoids- wide bore capillaries with large gaps allowing whole molecules and cells through. Eg. spleen due to RBC production/cleaning, and liver where endothelium is interspersed with kupffer cells.
What are the two types of venules? Describe them
Postcapillary venules: drain capillary beds. No smooth muscle but often pericytes. Site of blood plasma, neutrophil, monocyte leakage during inflammation
Muscular venules: Larger, up to 2 layers smooth muscle. Characterised by thin wall relative to diameter, and bulging endothelial nuclei
What are the features of veins?
Conduct blood at low pressure, so have thin walls and large diameters
All three tunics reduced, but adventitia larger and media smaller
Never a well-developed IEL
Valves (infoldings of intima) prevent backflow. However, when standing still, this leaks through slowly, leading to a pressure of approx. 100mmHg in the feet. Skeletal muscle movement forces blood up, back through the veins
What is venous thrombosis?
The formation of a blood clot, usually in the deep veins of the lower extremity. If part of the clot breaks loose it becomes an embolus, likely to lodge in the pulmonary arterial tree. Small clots have few to no symptoms, large fatal
Caused by any event slowing blood flow, increasing coagulability or damaging the endothelium
What are varicose veins?
Superficial veins of the legs dilate enough so that valves do not meet, causing the veins to become swollen and torturous
What is the structure of lymphatic capillaries?
Blind ended tubes, made of endothelial cells tethered to CT with anchoring filaments. When the tissue swells, the anchoring filaments drag the tube open wider.
Lack basement membranes, increasing permeability
- Have large gap junctions to allow passage of proteins and whole cells
Describe the larger lymphatic vessels
Resemble veins, but with thinner walls and more valves
Lymph propelled through by contraction of smooth muscle around the vessel (triggered by its distension) or by its compression due to surrounding tissue
Most tissues (apart from CNS, cartilage, bone, placenta, cornea, teeth, thymus) contain lymphatics- these enter a lymph node containing lymphocytes etc. This means cancer is likely to establish a secondary tumor here
Eventually enters the bloodstream via the thoracic duct or right lymphatic duct
What effect is had by the fact that all myocytes are involved in every cardiac contraction?
There can be no additional recruitment of myocytes. As CO must be equal to venous return, there must be another way to modulate contraction to maintain higher CO levels.
How is CO increased?
Can increase heart rate, but only by 3x and with less strove volume each time (due to reduced filling time)
Can increase ventricular diameter with more blood
Can alter Ca2+ action with neurotransmitters or use drugs, to increase force of contraction
What is starling’s law of the heart?
An increase in end-diastolic ventricular volume increases the stoke volume via an immediate stretch-induced increase in contractility. This is because increased myocyte length increases force generated for conc. Ca2+
What is the force length relationship?
There is an optimal myocyte length to get the maximum force of contraction. When the myocyte is too short it can’t shorten enough, and when too long it can’t make enough cross bridges.
Describe the force-frequency relationship
At higher heart rates, there is a higher force produced. This is due to the reduction in time for Ca2+ extrusion. The NCX exchange is impaired, increasing the Na2+ and Ca2+ in the cell, allowing the SR to be loaded more. On subsequent contractions, more Ca2+ is available to leave the SR. Therefore, the Ca2+ transient increases
In heart failure, increased heart rate leads to decreased force as Ca2+ is not taken back up into the cell, meaning Ca2+ transients remain constant in spite of HR increase
What are the effects of B-adrenergic drugs?
They stimulate adenylyl cyclase, increasing cAMP levels. This activates proteins kinases, which phosphorylate other proteins. This results in:
- Decreased Ca2+ sensitivity due to troponin I phosphorylation (although this is compensated by increased Ca2+ transient)
- Increased internal Ca2+
- Enhanced SR Ca2+ ATPase
- Altered RyR gating
How does Ca2+ concentration affect force of contraction?
It depends on [Ca2+] internal and total- although in a sigmoidal, not linear, fashion. To change strength of contraction we need to change either the Ca2+ transient (amount of Ca2+) or else the sensitivity to Ca2+ (force produced at a given Ca2+ level)
The Hill coefficient reflects the steepness of the curve
What factors affect Ca2+ in the heart?
Acidity (acidic environment causes less Ca2+)
Length (increased length increases Ca2+)
Catecholamines (increased catecholamines decrease Ca2+)
ATP (increased ATP decreases Ca2+)
Caffeine (increase caffeine increases Ca2+)
Inorganic phosphate (increased IOP decreases Ca2+)
What happens to [Ca2+] in increasing an decreasing pH?
At acidic pHs, the Na+/H+ exchanger works on removing H+ from the cell in exchange for Na+. This reduces Ca2+ transient. At high pHs, the CHE and CBE transporters load acid into the cell.
What occurs during heart failure in terms of the Ca2+ transient?
The myocytes are more sensitive to Ca2+, and so increase force- although they are less able to relax, and so pump less blood.
What is the difference between immediate and slow responses to stretch in the heart?
Immediate: Increase Ca2+ sensitivity
Slow: Increased calcium transient.
This means that when stimulus frequency increases, the force of contraction also increases
What effects do the autonomic nervous system have on force of heart contraction?
PSNS: Decreased SA node firing so decreased force
SNS: Increased SA rate, resulting in increased Ca2+ influx, increased SR pump rate and decreased sensitivity of troponin to Ca2+ (to allow relaxation)
What are some drugs we can use to affect the heart’s contractility?
- Cardiotonic steroids: Increase Na+ by inhibiting their pump. This reduces Ca2+ extrusion
- Bipyridines: Increase cAMP (act like B adrenergic activators)
- Heart failure: Increased dimesion so decreased efficiency- most try to decrease filling pressures by giving vasodilators (NO), ACE inhibitors and diuretics
What is the effect of Ca2+ sparks on the rhythm of the heart?
They promote Ca2+ extrusion by the NCX pump. causing localized and potentially cell wide depolarization. As a consequence, they may trigger random APs
What happens to calcium transient if the Na+/K+ pump is decreased?
Increased intracellular Na2+, which slows or reverses the Na+/Ca2+ exchanger- so more Ca2+ in the cell
What is the problem with classifying disease symptoms into ‘has’ or ‘doesn’t have’?
Symptoms are a continuum, and are not always set out in a black and white cutoff
Additionally, depending on additional risk factors, such as age, smoking, weight, blood glucose, cholesterol, the interpretation of the result is different.
Ie. someone with 150/100 blood pressure may be at less risk than someone with 120/80 blood pressure who smokes.
How do we measure cholesterol? How does this differ to how we measure the efficacy of cholesterol-lowering drugs?
Cholesterol itself is measured in total cholesterol- including both high and low density cholesterol. By itself it isn’t really a useful measurement. We should be measuring the ratio of low to high density cholesterol
However, the efficiacy of cholesterol lowering drugs is equatable to measuring only LDL cholesterol, as it is only this type of cholesterol that changes.
Describe atrial contraction
It starts soon after the P wave, and ventricular volume is topped up by atrial contraction (although this is not necessary at normal heart rates)
Describe isovolumic contraction?
Onset is at R wave peak. Ventricular volume remains unchanged and first heart sound occurs. Takes place between start of systole and opening of semilunar valves
Describe rapid ejection
Semilunar valves open, with a rapid increase in aortic flow and venous and aortic pressure. Causes a rapid decrease in LV volume and atrial pressure due to the base moving to the apex and stretching the atria
Describe reduced ejection
- The runoff from the aorta to the periphery exceeds the LV output, so aortic pressure and flow drop. Aortic pressure is just greater than LV pressure so the blood keeps moving forwards. At the end of ejection, 55-75% of blood remains
What is isovolumic relaxation?
The aortic valve closes due to pressure gradient reversal- there is a slow backflow producing an incisura (notch) in the aortic pressure curve. The second heart sound occurs due to semilunar valve closure and while volume remains the same, LV pressure falls rapidly (although aortic pressure remains high.
Describe rapid filling
LV pressure is below LA pressure, allowing the AV valve to open and cause a rapid LV volume increase. The third heart sound is sometimes heard here
Describe slow filling
This is diastasis, where pressure are aqualized and there is a slow rise in atrial and venous pressures
What are the venous pulse waves?
a: a retrograde pulse into the jugular vein when the atria contract
- c wave: early phase of ventricular systole
- v wave: a gradual pressure increase during reduced ejection and isovolumic relaxation
What do echocardiograms show?
Wall thickness and valve motion, as movement changes the placement of black and white strips (representing muscle and and space).
What are the overall differences in pressure and valve sequence between the RHS and LHS of the heart?
The right ventricle has lower pressures as it pumps through the low-resistance lungs, rather than the entire systemic circuit. The right side valves open earlier and close later than the left side valves.
What causes the four heart sounds?
First heart sound is due to AV valve closure, and is of low frequency. Although the two sides close asynchronously, there is normally only one sound heard
The second sound is due to semilunar valve closure, and is of higher frequency. Sometimes it can be split due to aortic/pulmonary delay
The third heart sound can be heard in rapid filling
The fourth sound can be caused by oscillation and stretch during atrial contraction
How do you measure pressures in the heart?
- LA pressure obtained with a catheter with a balloon on the end (deflated)
- RA, RV and Pulmonary artery pressures are measured the same way, with the balloon inflated.
The balloon can be threaded further into the pulmonary artery until it wedges, and so the pressure here can be approximated as LA pressure
How do you measure cardiac output?
- The fick method: Q = O2 added to blood in lungs / venous O1-arterial O2 Q = VO2/PaO2-PvO2
- Thermodilution: A catheter is threaded through the RA and RV, with a temperature sensor in the pulmonary trunk. Cold saline is injected into the RA, and the change in temperature reaching the artery is measured. This means that there is no arterial puncture, toxicity or recirculation
How do you measure vascular resistance?
General: R = P1-P2 / Q
Total peripheral vascular resistance: TPVR = Psyst. artery - P syst. vein / !
Pulmonary vascular resistance; P (pul art) - P (LA) / Q
What is vasovagal syncope?
A failure of the body to maintain sympathetic activity- vagal activity increases dramatically and HR and BP decrease and fainting occurs
What is the functional consequence of the body being able to activate the SNS in only certain parts of the body?
Means that you can control what is activated- ie. in disease there is increased sympathetic stimulation to the heart, muscle and kidneys,
Where in the body does the parasympathetic vs. sympathetic nervous system run?
The parasympathetic system begins in the brainstem and runs down through the neck or into the head to innervate. Similarly, innervation to the bladder/genitals begins in the sacrum.
The sympathetic system has a trunk of ganglia, so the nerves leave the spinal cord and run into the ganglion chain, where they run up and down the body. This means that only some fibres run through the neck
The parasympathetic nervous system has long preganglionic fibres and short postganglionic fibres, while the sympathetic ganglia is vice versa
What are the neurotransmitter and receptors used in the parasympathetic nervous system?
1: Ganglion: Receptor in N2, uses ACh. Effector tissue: Muscarinic receptor, uses ACh
What are the neurotransmitters and receptors used in the sympathetic nervous system?
To Smooth muscle, cardiac muscle, gland:
Ganglion: Uses ACh on N2 receptor. Norepinephrine to alpha.beta receptor on target cells
To adrenal medulla: Chromaffin cell: ACh on N2 receptor. Epinephrine on Alpha/beta receptor on target cells
