Cardiovascular Flashcards
Write down the equation of systemic vascular resistance (SVR).
SVR = (MAP - CVP)/CO x 80
80 converts the unit from wood unit (mmhg/L/min) to metric (dynes/sec/cm-5)
Write down the equation of pulmonary vascular resistance (PVR).
PVR = (MPAP - PAWP)/CO x 80
80 converts the unit from wood unit (mmhg/L/min) to metric (dynes/sec/cm-5)
What is the terminal arterioles called?
Metarterioles
What are the two theories about acute local blood flow control in respond to metabolic need?
1) Vasodilator substance theory
When there is increased tissue metabolism or presence of oxygen deficiency, the tissue will release vasodilator substances (e.g. adenosine***, CO2, hydrogen ion, potassium ion, histamine). This substance will diffuse locally and cause local vasodilation
2) Oxygen demand theory
Smooth muscles need oxygen to contract. When there is increased metabolism and oxygen deficiency, vascular smooth muscle cannot constrict which lead to local vasodilation
*Reactive hyperemia vs Active hyperemia
Within a range of arterial blood pressure, the body is able to maintain local blood flow within a certain range. This is called Autoregulation. What are the two theories about autoregulation?
1) Metabolic theory
- Oxygen and nutrient deficiency → increase vasodilator substances → increase blood flow
- Too much oxygen & nutrient & blood flow → wash out vasodilator substances → vasoconstriction
2) Myogenic theory
- Stretch-induced vascular depolarization → Increase intracellular calcium…etc → vasoconstriction
- Metabolic factors appear to override the myogenic mechanism in circumstances in which the metabolic demands of the tissues are significantly increased
What is NO synthesized from?
L-Arginine
O2 + L-Arginine → NO + L-Citrulline (via NOS)
What is the half-life of NO?
6 seconds
Explain how NO causes vasodilation (2 mechanisms)
1) NO activates guanylate cyclase → converts cGTP to cGMP (important second messenger) → cGMP activates cGMP-dependent protein kinase → vasodilation
2) activates and opens KsubCa channels (via nitrosylation) –> outward flow of K –> hyperpolarization
What stimulates eNOS?
1) Shear stress
2) Vasoactive substances (e.g. acetylcholine, bradykinin, adenosine, substance-P)
3) Angiotensin II (usually it is a vasoconstrictor but this is a mechanism to protect for excessive vasoconstriction)
True or False: Angiotensin II, a potent vasoconstrictor, can stimulate NO production.
True
What is iNOS?
It is inducible nitric oxide synthase. It does not express in resting cells and needs to be induced by cytokines or microbial products.
Does increased potassium level cause vasoconstriction or vasodilation?
Vasodilation
How does methylene blue cause vasoconstriction?
It inhibits the NO/cGMP pathway
Does increased magnesium level cause vasoconstriction or vasodilation?
Vasodilaiton
Does increased calcium level cause vasoconstriction or vasodilation?
Vasoconstriction
Does increase plasma hydrogen ion concentration cause vasoconstriction or vasodilation?
Mild arterial vasodilation
Does increase plasma CO2 concentration cause vasoconstriction or vasodilation?
Moderate vasodilation peripherally, marked vasodilation in the brain
In pulmonary circulation is the opposite where increased CO2 causes vasoconstriction
Define mean systemic filling pressure.
The pressure in the systemic circulation when there is no flow. It is composed of unstressed volume and stress volume.
What is the formula for venous return?
Venous return = [(Mean systemic filling pressure - right atrial pressure)/Venous resistance]
Describe Frank-Starling curve.
Within certain range, the increased left ventricular end diastolic volume will increase the stroke volume due to the stretch of the myocytes leading to more forceful contraction.
* The foundation concept of fluid responsiveness*
- x axis: left ventricular end diastolic volume (preload)
- y axis: stroke volume (or cardiac output)
What is the formula for shock index?
Shock index = HR/SBP
What is the shock index to differentiate shock and normal dog?
SI ≥ 0.9 → shock
Which electrolyte abnormality is associated with U wave?
Hypokalemia
True or False: Hypokalemia leaves the myocardium refractory to the effects of class I antiarrhythmic agents (e.g. lidocaine)
True
In hypokalemia, the hyperpolarized state of cardiac cells means that a larger fraction of sodium channels remains in a resting state rather than an inactivated state. Class I antiarrhythmic drugs are more effective at blocking sodium channels that are in the inactivated state. Therefore, with fewer sodium channels in the inactivated state during hypokalemia, these drugs are less effective.
Lidocaine is more effective with low pH and hyperkalemia
True: ideal anti-arrhythmic for damaged myocardial tissue
What is normal arterial oxygen content?
20 ml/dL
What is normal cardiac output in dogs and cats?
Dog: 125-200 ml/kg/min
Cat: 120 ml/kg/min
What is normal oxygen extraction ratio?
20-30%
What is normal DO2 and VO2?
DO2: 20-35 ml/kg/min
VO2: 4-11 ml/kg/min
What is the definition of hypotension?
SAP < 90 mmHg or MAP < 60 mmHg
What are the 4 organ systems affected by hypertension?
Renal
Eyes
Cardiovascular
CNS
When you are able to palpate the femoral pulses, what is the estimated SAP?
> 60 mmHg
What is the estimated SAP when you can palpate the dorsal pedal pulses?
> 90 mmHg
What blood pressure is Doppler measured? SAP, MAP or DAP?
SAP
During Doppler blood pressure measurement, if the limb with the cuff is below the RA, does that cause falsely lower or higher BP?
Falsely higher
When the limb is below the level of the heart (and specifically the right atrium), gravity causes an increase in hydrostatic pressure in the blood vessels of the lower limb. This increased pressure adds to the actual blood pressure and is detected by the cuff, leading to a higher reading than the true systemic blood pressure.
- Limb below RA: Causes a falsely higher BP reading.
- Limb above RA: Would cause a falsely lower BP reading.
What is the most reliable reading from standard oscillometry BP measuring?
MAP
What is the difference between High-definition oscillometry and standard oscillometry?
1) HDO can measure more accurately in a wider range
2) HDO can obtain a more accurate reading in the presence of arrhythmias
3) HDO can obtain SAP, MAP and DAP
HDO devices perform realtime analysis of arterial wall oscillations to obtain pressure wave amplitudes →
Fill in the pressure within each camber & vessel.
Describe how to set up a continuous arterial blood pressure monitoring system
1) Place an arterial line
2) Prepare a bag of 1L saline with heparin (1-2U/ml), a transducer, a monitor and non-compliant arterial line monitoring extension tube. Attach them together.
3) Fill the entire arterial monitoring system with heparinized saline.
4) Attach the arterial BP monitoring system to the arterial catheter and the monitor.
5) There should be a 3-way stopcock on the arterial BP monitoring system. Turn it to close the patient end and open the monitor end to the atmosphere. Keep the system at the level of RA and zero the system.
6) After the system is zero. Turn the 2-way stopcock to close the opening to the atmosphere and connect the monitor to the patient. You should be able to obtain the arterial waveform.
7) Perform a fast flush test to determine if it is necessary to adjust the system and optimize its dynamic’s response
What are the 3 important steps for arterial BP transducer setup?
1) Zeroing
2) Calibration
3) Leveling
Is CVP close to right ventricular systolic pressure or right ventricular diastolic pressure?
RV diastolic pressure (= filling pressure of right side of the heart)
What is normal CVP?
0 - 5 cmH2O
What are the 3 main factors that can affect CVP?
1) Venous return
- Circulating blood volume
- Venous wall compliance
2) Right-sided cardiac diseases
3) Intrathoracic/intraperitoneal pressure
When the CVP is low, what are the two main differential?
Vasodilation (venodilation)
Decreased systemic circulating blood volume
When the CVP is normal, beside normovolemia, what are the two other possibilities?
Compensated hypovolemia
Compensated hypervolemia
List 10 differentials for elevated CVP
1) Hypervolemia
2) Systemic hypertension or marked vasoconstriction
3) Occlusion of the catheter
4) Right sided cardiac disease (e.g. tricuspid regurgitation, right sided systolic dysfunction)
5) Pulmonary hypertension
6) Pericardial effusion
7) Pneumothorax
8) Marked ascitis
9) Pleural effusion
10) Mechanical ventilation (PEEP)
11) Intrathoracic mass
When we place an intravscular catheter for pressure measuring, ideally the catheter should not occupy more than ___% of the lumen. What is that number?
10
How many cmH2O equals 1 mmHg?
1.36 cmH2O = 1 mmHg
When the animal is in sternal recumbency, how do you estimate the height of RA during the leveling or CVP transducer?
Draw a vertical line from sternum to the top of spinous process caudal to the scapula. The RA is at about 40% of the height of the line.
Describe how is the arterial waveform generated?
When the pressure waves go through the vessels, the reflection will create multiple oscillating waves with different frequency and amplutide (Fourior series). The arterial waveform is the summation of those oscillating waves
This is arterial blood pressure waveforms. Name 1-6.
1: Systolic upstroke
2: Systolic peak pressure
3: Systolic decline
4: Dicrotic notch (incisura)
5: Diastolic runoff
6: End-diastolic pressure
Explain how Dicrotic notch is created.
The elastic recoil of the arteries with the closed aortic valves cause a slight and transient increase of the arterial blood pressure.
In an arterial BP waveform, which part indicate MAP?
The shaded area beneath the arterial pressure curve
List 5 factors that can affect the patient’s direct arterial BP monitoring reading.
1) System’s dynamic response
2) Presence of air bubbles in the tubing
3) Respiration
4) Arrhythmias
5) Catheter location/placement
What are the two major components when it comes to a ABP monitoring system’s dynamic response.
1) Natural frequency
2) Damping coefficient
- They are determined by the system’s physical properties, specifically mass, elasticity, and friction
What happen when the natural frequency of the ABP monitoring system coincides with the natural ABP’s frequency?
The reading and the waveform will be exaggerated due to summation of the waveforms (“summation effect”) → higher SAP and lower DAP → overshooting, ringing
When the natural frequency of an ABP monitoring system is not adequate, it’s usually too low or too high?
Too low
- Ideally need to > 12 Hz or as high as possible
What does damping mean in the ABP monitoring?
Loss of the pulse pressure energy when the waves travel from the catheter to the transducer.
List 4 causes of damping in ABP monitoring.
1) Friction resistance along the line
2) Absorption of energy by the tubing and system
3) Air bubbles
4) Line occlusion
Does the higher damping coefficient mean more likely to overdamp or underdamp?
Higher damping coefficient → more significant of the damping → overdamp
What can we see in overdamped and underdamped arterial waveforms?
Overdamped: loss of details (e.g. dicrotic notch), slurred waveform
Underdamped: falsely high SAP and falsely low DAP, extra spikes and details that are non-physiological
What is the natural frequency of this ABP monitoring system?
25/1.7 = 14.7 Hz
- Note the number of blocks between oscillation peaks
Describe how to determine the damping coefficient with this figure.
17/24 = 0.71 (amplitude ratio)
According to the chart, the damping coefficient is 0.11
- Measure the length of two successive oscillations (i.e., from peak to valley, and from that same valley to the next peak).
How many oscillations after the fast flush in the fast flush test will be considered underdamping?
> 2 oscillations
- Normally should be 2 oscillations
Does air bubbles cause underdamp or overdamp?
- Very small air bubble may cause underdamp (act as a spring as they compress and decompress easily. This allows the pressure waveform to oscillate excessively, leading to an amplified or exaggerated response)
- Large bubble will cause overdamp (acts like a cushion, absorbing and dissipating the energy of the wave rather than transmitting it accurately to the transducer)
As the arterial waveforms move from central to peripheral, does the systolic peak gets higher or lower? What about the end-diastolic pressure?
Initial upstroke becomes steeper
Systolic peak gets higher
End-diastolic pressure gets lower
- The waveform is delayed; the dicrotic notch appears later and appears more slurred
- distal pulse amplification
During mechanical ventilation, does the pulse pressure decrease or increase during inspiration?
Increase
- The opposite during spontaneous ventilation
What are the three hallmarks for arterial waveforms in aortic stenosis?
1) Systolic upstroke becomes less steep
2) Loss of dicrotic notch
3) The systolic peak pressure may decrease in severe case
What are the three hallmarks for arterial waveforms in aortic regurgitation?
1) Very steep systolic upstrokes
2) Increased pulse pressure
3) Decreased end-diastolic pressure
Explain what Corrigan pulse is and list four conditions that we may observe it clinically.
Corrigan’s pulses is the rapid elevated and collapse pulse (increased pulse pressure but very short duration for each pules).
Aortic regurgitation, PDA, severe anemia, hypertension
When the ABP monitoring shows hypotension, list 5 steps you would do to check it.
1) Examine the patient to see if the patient’s clinical signs fit hypotension
2) Check the ABP tubing to see if there is any kink, blood clot or air bubbles
3) Check the pressured fluid bag to make sure the pressure is higher than 250 mmHg
4) Check if the arterial catheter is patent
5) Check if the patient’s position has change and if re-zeroing is needed.
Describe how to set up a CVP monitoring system (with water manometer).
1) Flush the patient’s central venous catheter with heparinized saline to make sure it’s patent
2) Keep the water manometer vertical (can use an IV pole). Collect the three way stopcock with manometer, fluid set and tubing toward the CVC (do not connect yet)
3) Close the manometer end. Fill the entire non-compliant tubing with normal saline. Connect the tubing to CVC.
4) Close the patient end. Fill the water manometer with 10-20 cm of normal saline
5) Keep the zero marker of the water manometer at the level of right atrium.
5) Close the fluid set end. Allow the water manometer and patient’s end to equilibrate.
how many percentage of systemic blood volume is in the venous system?
65%
What is the formula for transmural pressure?
Transmural pressure = intravascular pressure - extravascular pressure
When using CVP to assess volume responsiveness, what is expected to see in euvolemic patient (i.e. how many cmH2O CVP will increase? how long does it take to return to baseline?)?
CVP usually will increase 2-5 cmH2O and will return to baseline after 15 min
- Hypovolemic patient → CVP rises minimally or rapidly returns to baseline
- CVP takes longer to return to baseline → volume overload, cardiac dysfunction, restrictive pericardial disease
Name which cardiac cycle/phase are those waves and descents represent and what happen to the heart during that cycle/phase.
a wave: end-diastolic; right atrial contraction
c wave: early-systolic; isovolumetric ventricular contraction; tricuspid valves are pushed toward RA
x descent: mid-systolic; right atrial relaxation
v wave: end-systolic; systolic filling of RA (venous return)
y descent: early-diastolic; early ventricular filling
What is the formula to estimate CVP from the waveform?
CVP = (a wave peak + x descent base)/2
What change of CVP waveform can we see in patient with VPCs?
Cannon “a” wave
What change of CVP waveform can we see in patient with atrial fibrillation?
Absence of a wave and prominent c wave (due to overfilling of RA)
What change of CVP waveform can we see in patient with tricuspid regurgitation?
Broad, tall systolic c-v wave, beginning in early systole and obliterating the systolic x descent in atrial pressure.
Name the function of the Swan-Ganz catheter ports from top to bottom.
- Thermistor port
- Measure CVP (blue; proximal)
- Measure pulmonary artery pressure, collect sample for SvO2 (yellow)
- Drug administration port
- Balloon inflation port; measure PAWP (red)
Define preload and afterload.
Preload: a measure of the ventricular myocardium stretch at the end of diastole
Afterload: the force/resistance which the ventricles need to overcome to eject the blood
What is the formula for cardiac index?
Cardiac index (L/min/m2) = cardiac output/body surface area in m2
What is Fick’s principle and what is the formula modified from this principle to measure cardiac output?
Total uptake of the oxygen by the peripheral tissues equal the product of total blood flow through the tissues and the arteriovenous oxygen concentration difference.
- it can also be used for CO2 production
What is the formula when using CO2 rebreathing method to measure cardiac output
Although Fick’s method is the gold standard for CO monitoring, what are the major disadvantages?
- the patient is anesthetized and intubated to measure the VO2
- patient needs to be cardiovascularly stable
- not a real-time measurement as blood gas analysis is required
- requires a central line to have a mixed venous sample (PA)
Using the Fick’s method with CO2 production vs O2 consumption to determine CO
Patient is anaesthetised, intubated and hooked to a proprietary rebreathing circuit containing CO2. If CO2 significantly increases CO is high as more blood reaches peripheral tissues and carries more CO2 vs low CO2 exhaled = low CO and low tissue perfusion
When using thermodilution to measure cardiac output, where is the indicator (saline) injected and where is the dilution measured?
There are two methods:
- transpulmonary: injection via jugular vein and sampling on peripheral vessels (i.e. femoral artery)
- pulmonary artery Injection: injection and sensor within the PA
What is transesophageal echocardiography measured to evaluate the cardiac output?
Cross-section area of left ventricular outflow tract & aortic blood velocity
What is mean pulmonary artery pressure in dogs?
10-20mmHg
What is normal cardiac index in dogs?
3.5 - 5.5 L/min/m2
What is normal stroke volume in dogs?
1.5-2 ml/kg/beat
What is normal SVR and Pulmonary vascular resistance?
SVR: 0.5-0.8 mmHg/kg/min
PVR: 0.04-0.06 mmHg/kg/min
10x difference!
What is normal pulmonary arterial wedge pressure in dogs?
5-12 mmHg
List 7 potential errors that can cause inaccurate CO measurement when using thermodilution method.
- Arrhythmias
- Respiration (ideally measure at end-expiration)
- Intracardiac shunt
- Thermistor probe problems (malfunction, got blood clote)
- Severe hypotension
- Inadequate indicator injection
- Concurrent large volume fluid/med administration
For the CO measurement using CO2 rebreathing method, what is the name of the monitor? What is the formula used in this monitor to calculate CO?
NICO
- The equation is for partial rebreathing technique
This is the graphs for thermodilution result. Which one indicates low cardiac output, and which one indicates high cardiac output?
b) indicates high cardiac output
c) indicates low cardiac output
List 4 possible complications for thermodilution method.
1) valve damage, endocarditis
2) rupture of RA or PA
3) blood clot formation, air embolism
4) arrhythmias
What technique does PICCO use to measure CO?
Transpulmonary thermodilution
- Inject a cold fluid bolus in jugular vein and measure its changes in femoral artery
- It can also analyze the pulse waveform contour and therefore obtain more information (e.g. preload, afterload…etc)
How does LiDCO measure CO?
Inject a fixed dose of lithium chloride and then has a lithium-selective electrode placed at the peripheral arterial catheter
- It can also analyze the arterial pulse waveform
What are the two CO monitor system that integrate arterial waveform?
PiCCO
LiDCO
True or False: When using Fick’s principle to measure CO, the result won’t be accurate if there is a shunt.
True
Describe how to place a Swan-Ganz catheter.
1) Attach ECG to the patient
2) Clip and aseptically prepare the jugular vein. Fill the introducer with heparinized saline and Insert the introducing catheter.
3) Get the thermodilution catheter and attach **distal port to pressure transducer **via a three-way stopcock and flush the system with heparinized saline.
4) Attach continuous flush line to the transducer and pressurize the bag to ≥200 mm Hg.
5) Zero the pressure transducer.
6) Insert the thermodilution catheter through the introducer catheter to about 20 cm and verify that the pressure tracing reflects a central venous pressure waveform.
7) Advance the catheter with the natural curve of the catheter aimed toward the sternum of the animal; watch for a typical ventricular waveform.
8) If the catheter advances to the **50-cm mark **without entering the right ventricle, withdraw it to the 20-cm mark and start again.
9) If the pressure tracing becomes damped, flush the distal port with the transducer’s fast flush device; if the pressure tracing abruptly ceases followed by a rapid, linear increase, the end-hole has butted up against a vessel or heart chamber wall and should be withdrawn slightly and then reinserted.
10) Once the catheter tip has entered the right ventricle, inflate the balloon with 1 mL of air and advance it further until the pressure waveform indicates that the catheter tip has entered the pulmonary artery.
11) With the balloon inflated, advance the catheter until the pressure tracing reflects occlusion of a branch of the pulmonary artery; deflate the balloon and verify a good pulmonary artery tracing.
12) Bandage the catheter and introducer set aseptically and occlusively.
What is normal arterial and venous oxygen content in dogs?
Arterial: 17.8 ml/dL
Venous: 14.2 ml/dL
As the Swan-Ganz catheter enters the heart and advances slowly, what are the pressure waveform change do you expect to see? Order them from the beginning to the end.
C → D → A → B
Comparing the PAWP and CVP, the c wave is more difficult to discern in PAWP. List 2 reasons to explain why.
- Damping when the waveform travels from LA to pulmonary artery
- ## There is shorter time between LA contraction and LV contraction compared to RA & RV contraction → a & c waves may superimposed
List 4 ECG abnormalities that can be seen in hypokalemic patient.
1) Atrial/ventricular tachyarrhythmias
2) Prolonged QT interval
3) Decreased T wave amplitude
4) ST segment elevation/depression
What is the ECG abnormalities that can be seen in hypocalcemia?
Prolong QT interval
- If hypercalcemia → shortening of QT interval
When patient experiences hypertension crisis, how fast shouldn’t the BP drop?
No more than 25% in 1 hour
What is the formula for Reynold’s number? What is it used for?
It is used to evaluate the tendency of turbulence to occur
What is the cutoff of Reynold’s number for the turbulence at the branch of vessels?
200-400
What is the cutoff of Reynold’s number for definitive turbulence no matter branch or smooth vessel?
> 2000
What is the formula for Poiseuille’s law?
In the systemic circulation, where do most of the systemic resistance occur?
Small arterioles (2/3 of total resistance)
Between what blood pressure range can the blood vessels maintain relatively constant flow rate via autoregulation?
75 - 175 mmHg
True or False: Pulse pressure = Stroke volume/arterial compliance.
True
Name 3 blood reservoirs.
1) Spleen
2) Liver
3) Large intra-abdominal veins
4) Venous plexus under the skin
True or False: Lymph from the entire body all flows into the thoracic duct, which empties the lymph into the venous system at the junction of left internal jugular vein and left subclavian vein.
False.
The lymph from right side of the neck and head, right arm, and parts of the right thorax flows into the right lymph duct → right subclavian vein and internal jugular vein
Where does vasomotor center locate?
Medulla and lower 1/3 of the pons
True or False: Under normal condition, there is continuous partial constriction of blood vessels caused by sympathetic nerve. This is called vasomotor tone.
True
True or False: The vasomotor center can not only control vascular tone but also the heart rate.
True
From Guyton: “The lateral portions of the vasomotor center tran mit excitatory impulses through the sympathetic nerve fibers to the heart when there is a need to increase heart rate and contractility. Conversely, when there is a need to decrease heart pumping, the medial portion of the vasomotor center sends signals to the adjacent dorsal motor nuclei of the vagus nerves, which then transmit parasympathetic impulses through the vagus nerves to the heart to decrease heart rate and heart contractility.”
True or False: The baroreceptors response is linear to the blood pressure.
False
When BP below 50-60 mmHg, baroreceptors at the carotid sinus do not respond.
When BP below 80 mmHg, baroreceptors at the aortic arch do not respond.
Explain how the circulatory reflex work after it is initiated by the activated baroreceptors.
The baroreceptor signal enters the vasomotor center → the secondary signal inhibits the vasoconstrictor center and stimulates the vagal parasympathetic center → vasodilation, decrease heart rate and contractility
List 3 conditions that will activate the chemoreceptors.
1) Low oxygen
2) High CO2
3) Increased H+ ion
Where do chemoreceptors locate?
2 carotid bodies locate at the carotid bifurcation; 1-3 aortic bodies locates adjacent to the aorta
List 3 mechanisms of how the low pressure baroreceptors (especially atrial receptors) regulate high blood volume.
Low-pressure receptors are stretch receptors in pulmonry artery, atria and vena cava. They respond to changes in blood volume.
1) decrease in SNS tone –> afferent renal vasodilation → increase GFR and fluid filtrated through the glomerulus
2) Decrease ADH release → decrease water reabsorption
3) Release atrial natriuretic peptide → decrease sodium and water reabsorption at the nephrons
4) Bainbridge reflex –> increased atrial stretch –> increase HR to avoid pooling of blood
Describe Bainbridege reflex.
Increased atrial pressure leads to increased heart rate and contractility.
- The afferent limb of the reflex within this signal, when activated takes sensory information from the vagus nerve to medulla oblongata, and the efferent limb sends out inhibitory signals by reducing vagus nerve tone and increasing the sympathetic outflow.
What is the reflex associated with the respiratory sinus arrhythmia?
Bainbridge reflex vs vagal reflex?
Inspiration → increased HR
Expiration → decreased HR
What happen to heart rate and BP during CNS ischemic response?
Increased sympathetic tone → HR and BP elevate
How will the cardiac output curve and venous return curve change during sympathetic stimulation?
When does the S1 heart sound happen?
When the mitral and tricuspid valves close
Isovolumetric contraction
When does the S2 heart sound happen?
When the aortic and pulmonic valves close
Isovolumetric relaxation
Explain the splitting S2.
S2 heart sound is composed of closing of aortic valve and closing of pulmonic valve. Aortic valve usually close very slightly before pulmonic valve.
During inspiration, the intrathoracic pressure decreased → increased venous return → more blood in the RV → pulmonic valve open for a bit longer because more RV volume → less blood return to LA → slightly decreased LV volume → aortic valve closes earlier due to shortening emptying time
What is S3 heart sound and when does it usually happen?
- It is also called ventricular gallop
- When mitral or tricuspid valves open and the blood is passively filling the ventricular → S3 is the sound when the large volume of blood strikes a very compliant ventricle
- Early diastole
- Often heard in dogs with DVM
What is S4 heart sound and when does it usually happen?
- It is also called atrial gallop
- When atria contracts to force the blood into a very non-compliant ventricle
- End diastole
- Often heard in cats with HCM
What is the resting membrane potential for ventricular myocardium? What about SA nodal cells?
Ventricular myocardium: -85 mV
SA nodal cells: -55 ~ -60 mV
Which one is RBBB and which is LBBB?
A: LBBB
B: RBBB
List 3 differences between myocardium and skeletal muscles.
1) action potential of myocardium is caused by fast sodium channels and L-type calcium channels; AP of skeletal muscles is caused by fast sodium channels only
2) The source of Ca in myocardium is from extracellular space; while in skeletal muscles it’s from endoplasmic reticulum
3) There is no plateau phase in skeletal muscle AP
Skeletal and myocardial muscle are _____ filament regulated while smooth muscle is ____ filament regulated
skeletal and myocardial muscles are THIN filament regulated (Calcium binding to troponin key step for shifting of tropomyosin interaction between actin and myosin) vs smooth muscle requires Ca binding to calmodulin to activate MLCK which will phosphorilate myosin head and allow detachment from actin
Name each phase and describe how electrolytes move in each phase.
0: depolarization; fast Na channel open and close Kir channels
1: initial repolarization; fast Na channel close, transient outward K channel open (Kv channels ITO current), also Na/Ca exchanger open (Na from phase 0 exists while Ca starts to come in)
2: plateau; L-type Ca channel open, transient outward K channel close
3: rapid repolarization; L-type Ca channel close; slow and rapid dealyed K rectifier channel open
4: resting membrane potential; slow and fast delayed K rectifier channel closes, inward rectifier K channel open
In phase 0 which other channels are involved apart from fast Na?
Kir (K inward rectifiers) channels close - these are the one responsible to keep stable membrane potential
Desribe the two-gate structure of fast Na channels
“m” gate is voltage dependent
“h” gate is time dependent
The “m” gate opens when depolarization of the myocyte occurs while the ‘h’ gate closes to terminate Na entry a few millisecond after ‘m’ have opened.
‘h’ then remains close until the cell has partially repolarized –> responsible for absolute refractory period (protects the myocardium from tetany).
The ‘m’ gate closes at late phase 3 –> responsible for relative refractory period.
When the ‘m’ is close, but ‘h’ is open a cell receiving a strong enough stimulus can be depolarized again.
what are the three states of fast Na channels?
inactivated: ‘m’ open but ‘h’ close (absolute refractory period, phase 1,2 and early 3)
resting: ‘m’ close but ‘h’ open (late phase 3 and 4)
open: both ‘m’ and ‘h’ open (only 1-2 milliseconds during rapid depolarization, phase 0)
What is the funny current?
Ion current in pacemaker cells.
Inward flow of Na and outward flow of K via HCN channels (hyperpolarization cyclic nucleotide channels).
HCN channels sensitive to cAMP –> action of sympathetic nervous system and beta blockers on HR.
How does the PSN system decrease HR?
Activates KAch channels –> otward flow of K ions –> hyperpolarization of pacemaker cells
This channel is also acted upon by gamma subunit of Gi protein (A1 adenosine receptors and digoxin)
Which Ach receptors can be found in the myocardium? how do they work?
Muscarinic M2 receptors –> Gi coupled –> drop cAMP + activate KAch (gamma subunit) to hyperpolarize cell and pull the resting potential away from threshold
Describe how excitation-contraction coupling happens.
1) Action potential reaches the T tubules system which leads to depolarization
2) The voltage change will be sensed by dihydropyridine (DHP) receptors which link to the ryanodine receptor channels (Ca release channels) on the sarcoplasmic reticulum
3) The Ca release channels open and release many Ca ions and cause contraction
4) Ca ions are re-uptaken by active calcium channels called SERCA (sarcoplasmic reticulum Ca2+-ATPase). Ca ions are bound with calsequestrin in the sarcoplasmic reticulum
What is the main difference between myocardium and skeletal muscle excitation-contraction coupling process?
The Ca storage in the myocardium sarcoplasmic reticulum is not as abundant as skeletal muscles. The Ca ion inflow during the plateau phase of AP triggers the Ca release from the sarcoplasmic reticulum and the Ca from both extracellular fluid and SR cause muscle contraction
- Myocardial contractility is heavily dependent on the extracellular Ca ion concentration
During myocardial excitation-contraction coupling process, what are the two ways to lower Ca concentration in the cells?
1) SERCA2 (sarcoplasmic reticulum Ca2+-ATPase)
2) Na-Ca exchanger on the sacrolemma
Why does ‘rigor mortis’ occur?
Relaxation is an. ATP-dependent mechanism (Na/Ca exchanger and SERCA need ATP)
What is parvalbumin?
It is a negatively charged cytosolic protein that binds to Ca++ and chaperones it into the SR
This is part of the ‘sarcoplasmic calcium buffering system’
Draw the Wigger’s diagram.
How many percentage of blood in the ventricle is contributed by atrial filling?
20%
What is ejection fraction (EF) and what is the formula? What is normal EF in dogs and cats?
Ejection fraction is the fraction of the blood in the ventricular chamber that is ejected during systole in relation to the total blood volume during end-diastole
EF = SV/LVEDV
Normal EF in dogs and cats: 50-70%
What is the difference between LV and RV pressure.
RV is about 1/6 of LV
On the heart, where do the parasympathetic nerves innervate?
atria
How does SA node generate its self-excitation AP?
Slow Na channel is very leaky and can cause continuous slow Na inflow. When the membrane potential reaches -40 mV, L-type Ca channels open, causing depolarization and generation of AP.
Compare the waveforms, different phases and electrolytes movement in each phases between ventricular and SA nodal AP.
What is hepatojugular reflex and what does it indicate?
Hepatojugular reflex means when the pressure is applied on the liver, the jugular vein becomes distended.
Positive hepatojugular reflex means the heart cannot compensate with increased venous return.
According to ACVIM Consensus Statement, systemic hypertension has three categories, what are them?
Situational hypertension
- White coat hypertension
Secondary hypertension (most common)
Idiopathic hypertension
List 5 diseases process that can cause systemic hypertension in dogs and cats.
Cushing disease
Hyperthyroidism
Chronic kidney disease
AKI
Pheochromocytoma
DM
Primary hyperaldosteronism
Which is the most common first manifestation of SH?
The eyes are the most vulnerable organ for TOD.
First manifestation is tortuous retinal vessels followed by multifocal retinal oedema and exudative retinal detachment.
Early aggressive treatment can lead to physical retinal re-attachment but rarely resoration of vision.
Classification of hypertension based on TOD risk
What is the Renal Resistive Index?
Sonographic measure of blood flow resistance in arcuate arteries
RIR = (peak systolic velocity - peak diastolic velocity) / peak systolic velocity
RIR closely correlated with number of organ involved in TOD
RI>0.7 = 3-4 organs involved
What is PRES?
Posterior Reversible Encephalopathy syndrome
Form of acute hypertensive encephalitis - treat with nicardipine (CCB similar to amlodipine but injectable form).
Sudden increase in MAP overcomes autoregulation mechanism
What is the difference between hypertensive emergency and hypertensive urgency?
Hypertensive emergency SAP>180 and evidence of TOD vs hypertensive urgency SAP>180 without evidence of TOD
List 5 medications that can cause systemic hypertension in dogs and cats
Glucocorticoid
Vasopressin
Epinephrine
Phenylephrine
Minerocorticoid
EPO
Phenylpropranolamine
True or False: ACVIM Consensus Statement recommends routine screening of systemic hypertension in dogs and cats.
False
- Patients > 9yrs will be reasonable
According to ACVIM Consensus Statement, SBP above what is considered severe hypertension?
> 180 mmHg
According to ACVIM Consensus Statement, when the initial SBP is < 160mmHg, what is the recommended follow-up plan?
Recheck in 3-6 months
According to ACVIM Consensus Statement, when the initial SBP is between 160-179mmHg without TOD, what is the recommended follow-up plan?
Recheck twice in 8 weeks & recheck for TOD
If the SBP is still persistently above 160mmHg, antihypertensive therapy is recommended.
According to ACVIM Consensus Statement, when the initial SBP is > 180mmHg without TOD, what is the recommended follow-up plan?
Recheck twice in 14 days & recheck for TOD
If the SBP is still persistently above 160mmHg, antihypertensive therapy is recommended.
According to ACVIM Consensus Statement, what are the two main goals for antihypertensive therapy
1) Minimize the risk of TOD (SBP ≤ 140 mmHg; optimal goal)
2) Maintain the SBP ≤ 160 mmHg (minimal goal)
According to ACVIM Consensus Statement, when you start a anti-hypertensive therapy, what is the recommended follow-up plan?
Recheck BP in 7-10 days if no TOD
Recheck BP in 1-3 days if TOD presents
*If BP < 160 mmHg on recheck, the next recheck can be 4-6 months.
Why calcium channel blocker should not be used as a monotherapy in dogs for hypertension management?
Because calcium channel blockers mainly cause renal afferent arteriole dilation → may increase the glomerulus capillary hydrostatic pressure
What is the possible limitation of combining calcium channel blocker and ACE inhibitors or ARB for canine hypertension management?
Calcium channel blockers mainly cause renal afferent arteriole dilation; ACE inhibitors and ARB mainly cause renal efferent arteriole dilation → may not make much change of the glomerulus capillary hydrostatic pressure
What is the first choice of antihypertensive drugs for dogs and cats, respectively?
Dogs: ACE inhibitor
Cat: calcium channel blocker (because of established efficacy)
In cats with systemic hypertension, what is the key predictive factor for survival?
Proteinuria
According to ACVIM Consensus Statement, what is the recommended antihypertensive therapies for cats with hyperthyroidism?
Amlodipine
Beta blocker (atenolol > propanolol as selective Beta 1 blocker and safer for asthmatic cats)
What are the two criteria for systemic hypertension that indicate emergency intervention?
1) SBP > 180 mmHg
2) Signs consistent with intracranial TOD
What is the MOA for fenoldopam?
Dopamine-1 receptor agonist -> vasodilation
Dose: 0.1 μg/kg/min with careful (ie, at intervals of at least 10 minutes) monitoring of BP. The dosage can be titrated up by 0.1 μg/kg/min increments every 15 minutes to the desired SBP, to a maximal dosage of 1.6 μg/kg/min.
No evidence of clinical improvement of AKI in either dogs (0.8 ug/kg/min) or cats (0.5ug/kg/min).
What is the MOA for hydralazine?
Direct smooth muscle relaxant
SSAO (semicarbazide-sensitive amine oxidase) inhibitor.
Interferes with intracellular Ca metabolism. Prevents inititation and maintenance of contractile state in smooth muscle.
Specifically it is thought to interfere with IP3 receptor on SRS.
Dog: 0.1 mg/kg IV over 2 minutes, followed by a CRI of 1.5-5.0 μg/kg/min
Cat: 1.0-2.5 mg per cat SC
What is the main difference between nitroprusside and nitroglycerin?
Nitroprusside: arterial and venous dilators
Nutroglycerin: mainly venodilator
According to ACVIM Consensus Statement, what are the 5 types of cardiomyopathy phenotypes in cats?
1) Hypertrophic cardiomyopathy
2) Restrictive cardiomyopathy
- Endomyocardial form vs Myocardial form
3) Dilated cardiomyopathy
4) Arrhythmogenic cardiomyopathy
5) Nonspecific phenotype
What are the two cardiomyopathy phenotypes that can be caused by hyperthyroidism?
HCM, RCM (restrictive)
What are the staging and definition of cardiomyopathy in cats?
A: Predisposed
B1: Subclinical with low risk of developing CHF/ATE (normal, mild atrial enlargement)
B2: Subclinical with high risk of developing CHF/ATE (moderate, severe atrial enlargement)
C: Current/previous CHF/ATE
D: Refractory CHF
What is the prevalence of HCM in cats?
15%
- 29% in older cats
What is the 5-year cumulative mortality rate in cats with HCM?
23%
What are the breeds that are predisposed to HCM?
Maine Coon, Ragdoll, British Shorthair, Persian, Bengal, Sphynx, Norwegian Forest cat, Birman
According to ACVIM Consensus Statement, in cats with HCM, what are the markers of increased risk of CHF/ATE?
Gallop sound or arrhythmia on PE
Moderate to severe LA enlargement
Decreased LA fractional shortening (LA FS%)
Extreme LV hypertrophy
Decreased LV systolic function
Spontaneous echo-contrast or intracardiac thrombus
Regional wall thinning with hypokinesis
Restrictive diastolic filling pattern
True or False: Dynamic left ventricular outflow tract obstruction (DLVOTO) is a poor prognostic indicator in HCM cat.
False
True or False: A loud systolic murmur (grade 3-4/6) is more common in cats with HCM than in normal cats, but an increase in heart murmur intensity over time does not necessarily indicate the presence or worsening of disease.
True
What is the recommended treatment for cat with stage B1 HCM?
None
What is the recommended treatment for cat with stage B2 HCM?
thromboprophylaxis (e.g. clopidogrel; 18.75 mg/cat PO q24h, with food)
- If patient has rapid ventricular rate or AF → Diltiazem, atenolol or sotalol
What is the recommended treatment for cat with stage C HCM?
Diuretic
Thromboprophylaxis
Pimobendan may be considered if patient has poor contractility and absent of DLVOTO (or dobutamine CRI)
What is the recommended Torsamide dose in cats with CHF?
0.1-0.2 mg/kg PO q24h
What peak tricuspid regurgitation velocity make the probability of PH intermediate?
3.0 - 3.4 m/s
What is the MOA of sildenafil?
It is a phosphadiesterase type 5 inhibitor. Phosphadiesterase type 5 can degrade cGMP to 5’-GMP and decrease the NO vasodilatory function. By inhibiting cGMP degradation, it leads to vasodilation.
Describe how to measure Vertebral left atrial score and what is the normal range in dogs?
1) Draw a line from the centro-ventral carina to the most caudal aspect of left atria where it intersects with dorsal border of caudal vena cave on the lateral view.
2) Transport the line to the cranial edge of T4 vertebral body.
VLAS ≥ 3 → likely heart failure
List 4 mechanisms of abnormal calcium handling during CHF development.
1) Myosin isoform switching
2) Impaired Ca2+ transients and ryanodine function
3) Phospholamban upregulation
4) SERCA downregulation
What is the definition of P mitrale and P pulmonale?
P mitrale: P wave width >40 msec
- Usually seen in LA enlargement
P pulmonale: P wave height >0.5 mV
- Usually seen in RA enlargement
What is the difference on CVP waveform between constrictive pericardial disease and cardiac tamponade?
Both will show tall a and c wave.
In constrictive pericardial disease, the y descent will be tall (increased resistance to passive atrial filling)
In cardiac tamponade, the y descent will be almost absent (no flow to the atria as collapsed)
What dose the EDPVR imply?
End-diastolic ventricular pressure volume relationship
It implies ventricular compliance
What does ESPVR imply?
End-systolic ventricular pressure volume relationship
It implies inotropic state of the heart
What are the two main mechanisms that trigger atrial fibrillation?
- ectopic foci - usually at the junction between pulmonary vein and atrial tissue
- re-entry phenomenon - premature beat starts a local abnormal circuit (wavelet hypothesis)
What does this E/A ratio and shape indicate?
Impaired relaxation (grade 1 diastolic dysfunction)
If a patient has known diastolic dysfunction and this is the E/A ratio you see, what does it indicate?
Pseudonormal filling pattern (grade 2 diastolic dysfunction)
Progressive diastolic dysfunction causes LA pressure to rise. The latter increases the pressure gradient between the left atrium and the left ventricle and will act as a driving force to fill the ventricle during early diastole.
If a patient has known diastolic dysfunction and this is the E/A ratio you see, what does it indicate?
Restrictive filling pattern (grade 3 diastolic dysfunction)
A further increase in filling pressure will increase the gradient between the left atrium and the left ventricle during early diastole. The E-wave will become even taller and the A-wave shorter. The E/A ratio will be ≥ 2. In severe forms the A-wave may be so small as to be nearly invisible, and the E/A ratio may reach very high values of 5 or more.
What is happening? How to fix?
This is a failure to capture pacemaker issue - pacemaker spike not followed by qrs.
Adjust output (amplitude/time) to achieve threshold.
What is the MOA for Digoxin?
1) positive inotropic (by inhibiting Na-K ATPase → increased intracellular Na → increased intracellular Ca
2) Decreased AV conduction: vagomimic effect
Troponin and acidosis
In acidosis status troponin affinity for Ca++ is severely decreased.
This is why pimobendan is a very good drug choice.
What is Tetralogy of Fallot composed of?
Ventricular septal defect (VSD)
Overriding aorta
Pulmonary stenosis
Right ventricular hypertrophy
N.B. RV hypertrophy is secondary to “Eisenmenger physiology”. Initially L to R shunt due to interventricular septal defect, but due to pulmonary stenosis and high pressure on R side the shunt reverts to R to L
What is the MOA of ephedrine?
increase the release of NE from sympathetic nerve ending
How do the venous function curve and the cardiac function curve in: venodilation/venoconstriction, volume load/volume depletion, decrease/increase contractility, arteriole dilation/constriction
How does the PV loop change with changes in preload?
How does the PV loop change with changes in contractility
How does the PV loop change with changes in afterload?
Wiggers diagram with aortic stenosis
Wiggers diagram with mitral stenosis
Wiggers diagram with aortic regurgitation
Wiggers diagram with mitral valve regurgitation
What are the main types of norepinephrine receptors? where are they located respectively?
Junctional (or post-synaptic)
Pre-synaptic
Extrajunctional (binds to circulating norepi synthesised by adrernal medulla)
Explain internalization process after beta 1 and beta 2 stimulation
Both are Gs coupled –> PKA will phosphorylate beta-ARK protein which will uncople beta receptors and stimulate endocytosis. once recptor is in the vesicle it can either be recycled or degraded. Some internalised receptor bind to arrestin and start pathway that facilitate cardiac hypertrophy.
Fill in the following table
Describe the structure of potassium channels
quaternary protein(each type has a signature AA sequence) with a central pore in the intracellular side and selectivity filter on the extracellular side
N-pro-BNP test interpretation
Dogs with MMVD and a N-pro-BNP >1500 pmol/L more likely to develop overt CHF in the following 3-6 months
Dobermans >5y and N-pro-BNP >450 pmol/L high risk to develop DCM (even when still in occult phase)
List and briefly describe Rummel torniquet and Pringle manouver
These are two hemostatic techniques.
Rummel tourniquet uses umbilical tape placed underneath a vessel while the two upper ends get through a piece of tubing. Pull the ends protruding from tubing and clamp them to occlude the vessel.
Pringle manouver puts pressure on both hepatic artery and portal vein via the epiploic foramen
Definition of cardiogenic shock and mainstay of therapy
State of end-organ hypoperfusion due to the heart’s inability to deliver sufficient oxygen to tissues to meet metabolic demands in the presence of adequate intravascular volume.
Is this patient likely to be fluid-responsive?
Yes, it Y descend on the CVP waveform is very prominent.
In human a Y descend >4mm has been correlated to patients operating on the flat portion of the FS curve
