Term
Q1: What is the baroreflex system?
Q2: When there are changes in the MAP, what can the baroreflex system change in order to bring MAP back to normal? |
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Definition
A1: The baroreflex system is responsible for maintaining the Mean Arterial Pressure (MAP)
A2: When there are changes in the MAP, the baroreceptors will recognize this change and it bring MAP back to normal in 2 ways: 1) change cardiac output (CO) or 2) adjust the Total Peripheral Resistence (TPR) |
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Term
Q1: The average pressure in the arteries is called what?
Q2: Blood pressure in the right atrium is equivalent to what?
Q3: What is the Major determinant of TPR? |
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Definition
A1: Mean Arterial Pressure (MAP)
A2: It is equivalent to systemic venous pressure.
A3: the resistance of the systemic arterioles, which is inversely related to the radius of the vessels |
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Term
What is the function of the baroreflex system?
What is the equation for MAP? |
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Definition
The baroreflex system attempts to maintain MAP nearly constant by altering either CO or SVR
MAP = CO x TPR
MAP = (HR x SV) x TPR |
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Term
| What are the 2 forces that drive ion movement? |
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Definition
1.Electrical Force: the Membrane Potential
2.Chemical force: due to differences in ion concentration in the intracellular and extracellular fluid. AKA Nernst Potential |
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Term
The magnitude of an ion’s chemical force depends on what?
What is this equation called and what is the equation? |
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Definition
1.The ratio of extracellular and intracellular ion concentrations
2.The valence of the ion
Chemical potential is called the Nernst Potential:
Eion = (60/z) x log(Co/Ci)
Note: conductance of an ion does not affect the charge (conductance = speed) |
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Term
| Current is always defined in terms to the movement of what charge? |
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Definition
-the movement of POSITIVE charge (cation)
If the Positive (cationic) charge is moving OUT of the cell, we call that:
-Positive current
-Outward current
-Repolarizing current.
If the Positive (cationic) charge is moving INTO the cell, we call that:
-Negative current
-Inward current
-Depolarizing current. |
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Term
| What is the general rule about determing positive versus negative current? |
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Definition
-Positive currents make V (membrane potential) more negative (ie. Is K+ leaving cell, Cl- moving into cell)
-Negative currents make V more positive (ie. Na+ & Ca++ moving into the cell) |
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Term
| The magnitude of an ion’s current depends on what? |
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Definition
1.Forces driving ion movement: (V-E)
-Chemical force (Nernst potential)
-electrical force (membrane potential)
2. Conductance (g): how easily the ion can move across the membrane. |
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Term
| Conductance is referred to what? |
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Definition
Conductance is the ability of the ion to cross the cell membrane and is related to:
1.Number of open ion channels
2.Leaky channels
3.Ion concentration (this is important in hypokalemia and hyperkalemia) |
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Term
| What is the equation for current? |
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Definition
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Term
What is true about the equation for current?
I = g x (V – E) |
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Definition
1)If g is increased, V will always move closer to that ion’s Nernst potential (E).
2)If g is decreased, V will always move farther away from that ion’s Nernst potential (E)
3)Resting membrane potential will be closest to the Nernst potential (E) of the ion which has the greatest conductance (g). |
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Term
| In the condition of hyperkalemia, why would the threshold for depolarization be raised? |
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Definition
| When you have hyperkalemia, there is an increase in K+ outside the cell/there would be less K+ inside the cell so you would think that you are close to "threshold" however, it's not true because when the membrane potential is more positive, there will be LESS Na channels! THUS, you actually move the THRESHOLD to even MORE POSITIVE, so it takes much more cation moving in or anion moving out to hit depolarization! |
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Term
In a resting membrane, since V is closer to E of K than E of Na, and g of K is >>> g of Na…
How can I of Na = -I of K, if g of K >>> g of Na? |
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Definition
According to the equation: I = g x (V – E)
At resting membrane potential, (V-E) of K+ is small and g of K+ is large; while (V – E) of Na+ is large, and g of Na+ is small. As a result I of Na+ = -I of K+ |
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Term
| What are the equations associated with fractional conductance to K+ and Na+? |
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Definition
1) V = (fgk x Ek) + (fg na x Ena)
2) fgk = gk / (gk + gna)
Or fgna = gna / (gna + g)
3) if cell is only permeable to Na or K:
Fgna + fgk = 1 |
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Term
| The Golden Rule #1 of Electrophysiology is that the magnitude of the depolarizing current during the upstroke of the action potential (AP) will determine what? |
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Definition
1.Threshold potential
2.Amplitude of the AP
3.Rate of rise of the AP
4.Conduction velocity (CV): how quickly the AP propagates down the tissue |
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Term
| Golden Rule #2 is that the depolarizing current (I) is a Na+ current in nerve, skeletal muscle, and cardiac muscle . If the magnitude of the sodium current is decreased, then what? |
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Definition
1.Threshold potential is more positive (decreased excitability)
2.Amplitude of the AP is decreased
3.Rate of rise of the AP is decreased
4.Conduction velocity is decreased. |
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Term
Q1: Conduction velocity is how quickly an action potential propagates along a tissue. It is dependent on?
Q2: What are the 4 facts about the conduction velocity? |
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Definition
A1: It is dependent on the magnitude of the depolarizing current during the upstroke of the action potential.
A2:
1)When cations enter a cell during the upstroke of an action potential, the positive charges will repel and the cations will move to adjacent regions of the cell.
2)As positive cations accumulate in an adjacent region in front of the direction that the action potential is moving towards, membrane potential will be depolarized to threshold. An action potential will then occur in this region of the cell.
3)The greater the magnitude of the depolarizing current during the upstroke of the action potential, the faster cations will accumulate inside the cell and spread to adjacent regions (higher conduction velocity).
4)The action potential will only move in one direction down the tissue normally because the previously depolarized region is still in its refractory period (which we will discuss later). |
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Term
| Increasing Sympathetic firing to the heart will increase the heart due to? |
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Definition
1)Primarily by increasing the current (I) of funny channels in the SA node.
2)Increase in conduction velocity in the AV node (and decrease the P-R interval) |
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Term
Phase 4 in the SA node represents a balance between what two currents?
Increasing the funny currents (If) due to increase firing of SYM nerves will do what? |
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Definition
- It represents a balance between If and Ik.
1)Will make the maximal diastolic potential more positive (this is the most negative membrane potential that occurs in the SA node)
2)Make phase 4 more steep (threshold is reached sooner) |
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Term
| What is bizarre about Hypokalemia and Hyperkalemia? |
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Definition
In HYPOkalemia, there is less K+ outside the cell, so you would immediately think an INCREASE/Faster rate of depolarization; however, that is not the case because in hypokalemia, you actually get a decreased in conductance of K+, therefore, a decrease in K+ current, as a result, you get a longer AP (increase duration) because K+ cannot leave the cell very easily.
In HYPERkalemia, there is more K+ outside the cell, so you would immediately think a DECREASE/slower rate of depolarization; however, that is not true because in hyperkalemia, you get an increase in the conductance of K+, which will lead to an increase in K+ current (I), and therefore, you would get a shorter AP duration! |
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Term
| How come a cell cannot generate an AP regardless of the strength of the depolarizing stimulus during the Absolute Refractory Period? |
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Definition
A cell cannot generate an AP regardless of the strength during the absolute refractory period because the Inactivation gates are still closed. The inactivation gate will not open until it reaches near the Nernst potential for K+ again, which by then it will be open.
During the relative refractory period, the Na Inactivation gate will begin to open, during this time the cell could actually undergo another AP but it would need a much stronger stimulus.
As the cell membrane potential begin to reach threshold, the inactivation gate will begin to close; however, this gate is really slow and that is why you’re able to allow Na+ in. Na+ will come in and depolarize the cell until the inactivation gate closes again. |
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Term
| How does the ability of a nerve to fire an AP compare during its relative refractory period and during hypokalemia/hyperkalemia? |
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Definition
In both cases, the ability of the nerve to generate Ina (current of Na) is decreased which will result in:
1.More positive threshold
2.Decreased rate of rise of the AP
3.Decreased amplitude of the AP
4.Decreased conduction velocity
In both cases, the number of resting channels is lower than normal.
1.There has not been sufficient time to open all Na+ inactivation gates – due to relative refractory period.
2.Hypo/hyperkalemia – both cause a resting depolarization of resting membrane potential. As a result, repolarization stops before all inactivation gates have opened. This is known as INCOMPLETE REPOLARIZATION. |
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Term
| How does increasing plasma Ca++ recover excitability in a person with hyperkalemia? |
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Definition
-Increasing plasma Ca++ levels rapidly shifts both the Na+ inactivation and activation curves to more positive values.
-Raising Ca++ levels does not affect resting membrane potential: it will still be more positive than normal in a person with hyperkalemia (resting depolarization).
-However, shifting the Na+ inactivation curve to more positive values by raising Ca++ recovers more resting Na+ channels even at this more positive resting potential. (You give the Na+ channels more time to recover, and therefore, you’ll have more inactivation gates ready to open)
-This will increase Na+ current towards normal in the hyperkalemic person and therefore recover excitability in nerve, skeletal muscle, and cardiac muscle.
-After raising Ca++ levels to recover excitability, the hyperkalemia can then be corrected. |
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Term
| What will an increase in extracellular Ca++ levels do to excitability of nerve, skeletal muscle, and cardiac muscle in a person with normal extracellular K+ level? |
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Definition
-Increased extracellular Ca++ would shift the Na+ inactivation curve and the Na+ activation curve to more positive values.
-In a person with normal extracellular K+ level, the positive shift in the Na+ inactivation curve would not significantly increase the number of resting Na+ channels (since this person has normal resting potential).
-However, the positive shift in the Na+ activation curve would shift threshold to a more positive value.
**This would reduce excitability in this person |
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Term
| What is the difference between phase 4 of Hypo and Hyperkalemia? |
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Definition
Hypokalemia:
-MDP is more positive
-Phase 4 is more steep
-Tachycardia
Hyperkalemia:
-MDP is more negative
-phase 4 is less steep
-decreased rate of firing of the SA node (however, the baroreflex may increase SYM firing due to decrease cardiac output (therefore, you may not see brachycardia in hyperkalemia) |
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Term
| What are the effects of HYPERkalemia? |
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Definition
Resting potential & phase 0:
-Ek is less negative.
-resting potential depolarizes
-Na channels inactivate
-Rate of phase 0 depolarization decreases.
-Conduction velocity decrease
-QRS widens
Heart rate & phase 3:
-K-conductance increases
-Phase 2 duration decreases (QT interval decreases)
-Faster phase 3 repolarization (T-wave increases and becomes spike-like **Hallmark**
-in SA node, more negative maximum diastolic potential and slower phase 4 depolarization can produce bradycardia.
-baroreceptor reflex may blunt the direct effect hyperkalemia has on heart rate |
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Term
| What is the mechanism of action for reversal of Hyperkalemia? |
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Definition
-Calcium recovers resting Na channels by shifting Na-channel inactivation curve towards more positive potential.
-Na bicarbonate indirectly enhances Na-K pump by increasing the Na-Influx via the Na-H exchanger
-Insulin stimulates the Na-K pump
-Kayexalate enchances K-excretion by the kidney |
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Term
| What are the effects of Hypokalemia? |
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Definition
Resting potential & phase 0:
-Ek becomes more negative.
-Resting K-conductance also decreases.
-Resting potential depolarizes because the K-conductance effect exceeds the Ek effect.
-Sodium channels inactivate.
-Rate of phase 0 depolarization decreases.
-Conduction velocity decreases.
-**QRS widens.
Heart Rate & Phase 3:
-K-conductance decreases.
-Phase 2 duration increases (QT interval increases).
-**Slower phase 3 repolarization (T-wave flattens and splits to produce U-wave).
-In SA-node, more positive maximum diastolic potential and faster phase 4 depolarization can produce tachycardia.
-Baroreceptor reflex may blunt the direct effect hypokalemia has on heart rate |
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Term
What is Early After Depolarization?
What are EADs associated with?
Person with Hypo/hyper is more likely to have it? |
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Definition
Sympathetic Stimulation of Norepinephrine (NE) would affect Ca++ by shifting the activation curve towards more negative potential, which means that the activation gates begin to open sooner during depolarization.
Sympathetic stimulation (via NE) creates a larger Ca++ window. A potential problem created by this larger Ca window is that the inactivation gates may open before all activation gates have closed. if this happens, the cell would create a depolarizing current and move V more positive.
In a healthy person, larger Ca++ window produced by sympathetic stimulation does not create a problem because NE also increases the K+ current.
As a result, the rate of repolarization is increased compared to normal (seen as spiked T wave on the ECG).
-If K+ current is suppressed, EARLY AFTER DEPOLARIZATION (EAD) can occur in early phase 3 due to this Ca window.
EADs are associated with:
1. a decreased rate of repolarization (decreased K+ current)
2. Calcium window current due to opening of inactivation gates before activation gates have all closed.
3. Persons with Hypokalemia is more likely to have EAD because K+ conductance has been decreased in person with HYpoKal. |
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Term
| What are the conditions that favor Ca++ overload? (or Delayed After Depolarization, DAD) |
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Definition
-Tachycardia
-Increased current of Cal
-Suppression of Na-K pump leading to decreased calcium efflux via Na-Ca exchange.
Accordingly, DAD production is favored by high heart rates. An increase in intracellular sodium concentration (as produced by inhibition of the Na-K pump by cardiac glycosides) will reduce the ability of the Na-Ca exchanger to expel calcium from the cell during diastole. Indirectly, this will lead to more calcium moving into the sarcoplasmic reticulum. Although this is the mechanism by which cardiac glycosides increase contractility, it comes with increasing the risk of DADs. |
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Term
What are the requirements for reentrant conduction?
Reentrant loops are more likely to occur when? |
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Definition
1. A closed conduction loop.
2. Unidirectional conduction.
3. Action potential length < loop length.
Fribrillation results from the development of multiple reentry loops.
2. more likely to occur:
-conduction velocity is decreased
-duration of the AP is decreased. |
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Term
| What happens in a person experiencing hypoxia? |
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Definition
Insufficient O2 levels in the heart will decrease ATP formation.
The L-type Ca++ channel must be phosphorylated during each action potential in order to allow Ca++ to move through.
Decreased ATP will impair the Ca++ current which will decrease the duration of the action potential markedly.
Phase 4 resting membrane potential will be unchanged. |
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Term
| What happens in a person who experiences ischemia? |
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Definition
Ischemia (insufficient blood flow) will lower O2 levels in the heart and decrease ATP formation.
This will impair L-type Ca++ current during action potentials as occurs in hypoxia.
The decreased blood flow will also cause K+ to accumulate, resulting in local hyperkalemia.
This will cause a depolarization of resting membrane potential, so phase 4 resting membrane potential will be more positive (less negative) than normal.
Ischemia will impair Na+ current. |
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Term
| What are the equations used to calculate Total Body Water (TBW)? |
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Definition
TBW = Extracellular Fluid Volume + Intracellular Fluid Volume.
EFV = 0.25*plasma + 0.75*interstitial fluid volume
2 methods that are common used to calculate TBW:
1)TBW = 60% of BW(body weight)
2)TBW = 72% of LBM (lean body mass) |
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Term
| What are the 4 forces that affect the movement of H20 between Body Compartments? |
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Definition
1. Hydrostatic pressure
2. Osmotic Pressure (solutes in water causing pressure)
3. Oncotic Pressure (protein in water causing pressure)
4. Na-K pump (metabolic) - ion channels and transporters involved in cell volume regulation |
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Term
| What is the difference between Osmolality and Tonicity? |
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Definition
Osmolality: determined by the total concentration of solute molecules in solution. Osmolality has a chemical reference point.
Tonicity: defined by how the volume of cell changes when the cell is placed in the solution. Tonicity of a solution is the referenced to the effect the solution has on cell volume. Tonicity has a biological reference point.
-hypotonic: solution is very low in tone (solute), so water moves from outside the cell to inside the cell to balance the osmotic pressure, and the cell SWELLS
-hypertonic: solution is high in tone (solute), so water leaves the cell and the cell SHRINKS.
-Isotonic solution: Solution has the same concentration of solute as the cell, so the cell size does not change. |
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Term
| What is the rule to a Hypotonic Solution? |
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Definition
-A solution containing only permeant solutes will always be hypotonic regardless of the permeant solute concentration.
-A solution in which the osmolality due to impermeant solutes is less than the osmolality of the intracellular fluid (normally 290 mOsm) will be hypotonic regardless of the permeant solute concentration. |
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Term
| What is the rule to an Isotonic Solution? |
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Definition
-A solution containing only permeant solutes can never be isotonic regardless of the permeant solute concentration.
-A solution in which the osmolality due to impermeant solutes equals the osmolality of the intracellular fluid (normally 290 mOsm) will be isotonic regardless of the permeant solute concentration. |
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Term
| What is the rule to a Hypertonic Solution? |
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Definition
-A solution containing only permeant solutes can never be hypertonic regardless of the permeant solute concentration.
-A solution in which the osmolality due to impermeant solutes is greater than the osmolality of the intracellular fluid (normally 290 mOsm) will be hypertonic regardless of the permeant solute concentration. |
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Term
| What is the equation for Concentration of Impermeant Solutes in cell? |
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Definition
Conc. Of Impermeant Solutes in cell = (mass of Impermeant Solutes / cell volume)
Initial Conc x Initial cell volume = Final Conc x Final cell volume |
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Term
If you infuse Isotonic saline IV, will it cause a change in intracellular space?
If you infuse isotonic saline IV, how does saline reach the interstitial space? |
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Definition
1) no it will not change the intracellular volume.
2) Infusing saline IV will increase capillary pressure and promote filtration of fluid into the interstitial space. Saline will also decrease plasma protein concentration, which will decrease the oncotic force for reabsorption of fluid from the interstitial space. |
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Term
| What is hypovolemic Hyponatremia? What is the equation used to calculate Na deficit? |
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Definition
It is an electrolyte disorder.
Hypovolemic hyponatremia represents the condition where total body sodium is insufficient to maintain normal osmolality. Accordingly, the patient has a sodium deficit.
Na+ deficit = TBW x (desired [Na] – present [Na]) |
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Term
| What is hypernatremia? How is it calculated so that we can administer the proper amount of water to help our patient get back to normal osmolality? |
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Definition
The condition of hypernatremia represents the condition of a water deficit in relation to sodium content. In other words, body fluid osmolality could be returned to normal by adding water. The water deficit represents the volume of water that would have to be added to increase a person’s total body water to a normal value.
Water deficit = present TBW x { (current[Na] / Normal[Na]) – 1} |
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Term
| The magnitude of the depolarizing current affects four important characteristics of the Action Potential. If the depolarizing current is increased: |
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Definition
1. threshold is decreased (excitability is increased)
2. rate of rise of the action potential is increased
3. amplitude of the action potential is increased
4. conduction velocity is increased |
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Term
| What is MEA and is it fixed? Where would it mostly point? Can it be shift? List some |
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Definition
MEA is Mean Electrical Axis. The direction is expressed in degrees and the magnitude in millivolts (mV).
Changes in the position of the heart will influence the MEA. MEA is dependent on the balance of currents in the right and Left ventricles
The position of the heart can shift during:
-pregnancy (common)
-ventricular hypertrophy
-loss of tissue (myocardial infarction) |
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Term
| What is Right Axis deviation and Left Axis deviation? |
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Definition
A Right axis deviation has a MEA that is greater than +90 degrees.
A Left axis deviation has a MEA that is more negative than 0 or -30 degrees |
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Term
| What are the causes of Left Axis Deviation? |
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Definition
1. Left Ventricular Hypertrophy
-Systemic hypertension
-Aortic Stenosis (stiff valve)
2. Pregnancy (physically displaces the heart) |
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Term
| What are the causes of Right Axis Deviation? |
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Definition
1. Right ventricular hypertrophy
-Pulmonary hypertension (ie. Living in high altitude, low oxygen level causes vasoconstriction of pulmonary artery)
-Pulmonary stenosis (stiff valve)
2. Infarction of the left ventricle (loss of functional tissue in the left ventricle |
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Term
| What is the difference between 1st and 2nd degree AV node blocks as compared to 3rd degree AV node block? |
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Definition
First and second degree AV node blocks are incomplete blocks:
Ventricular depolarization is still triggered by action potential passing through AV node. QRS complex looks normal.
1st degree: Caused by reduced conduction velocity in the: AV node due to decreased calcium current atrium due to decreased sodium current.
2nd degree: Each P wave does not cause a QRS complex, but QRS complexes are caused by P waves.
Multiple P waves precede each QRS (integer ratio, 2:1 or 3:1)
Third degree AV node block is a complete block: depolarization of ventricles is completely independent of atrial depolarization.
The interval between the P wave preceding a QRS complex is getting progressively shorter (P waves are “marching through the QRS complex).
P waves are not causing QRS complexes (i.e., complete heart block).
The QRS complex looks normal which indicates that the ectopic focus for ventricular depolarization is near the distal portion of the AV node.
The wide QRS complexes (which reflect a longer time to fully depolarize the ventricles) indicate that the ectopic focus is in the lateral wall of a ventricle.
ECG looks like NON INTEGER. |
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Term
| What happens in premature ventricular depolarization? |
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Definition
There would not be a P wave preceding the QRS complex. Depolarization of the ventricle occurred due to an ectopic pacemaker within the ventricle.
The force of contraction would be decreased compared to normal since ventricular depolarization occurred slower than normal.
The wave may look upside down, which may indicate that there was not an ejection of blood, or very minimal ejection of blood out the ventricle. |
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Term
| ST Segment elevation or depression is a result of what? |
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Definition
An ischemic area in the ventricle causes an elevation or depression of the ST segment due to hyperkalemia in the ischemic area.
Insufficient blood flow to the area reduces ATP levels and so extracellular K+ levels rise due to reduced activity of the Na/K pump. Resting membrane potential in the ischemic area is more positive than the rest of the ventricle.
This difference in resting potential results in a current flow even before the ventricle depolarizes, and shifts the apparent isoelectric point on an ECG recording. |
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Term
| What is Ventricular fibrillation? |
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Definition
Ventricular fibrillation is a totally disorganized, chaotic ventricular rhythm due to multiple reentrant loops within the ventricles causing depolarization.
There is no effective cardiac contraction during ventricular fibrillation. This is a serious life-threatening situation due to the markedly reduced cardiac output.
Defibrillation is the treatment of choice for ventricular fibrillation. The rationale for this approach is that the electrical shock will cause the entire mass of myocardial cells to depolarize at the same time, and then be followed by spontaneous resumption of a supraventricular rhthym. Supraventricular means above the ventricle. |
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Term
| What is the equation for Stroke volume and Ejection fraction? |
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Definition
SV = EDV – ESV
Ejection Fraction (EF) = SV/EDV
Note: 0.5 to 0.7 is normal |
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Term
| What happens during Diastolic Filling? |
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Definition
a.When ventricular pressure falls below atrial pressure, the mitral valve opens and blood flows into the ventricle.
b.Rapid filling of the ventricle initially occurs with blood that had accumulated in the left atrium while the mitral valve was closed.
c.Atrial pressure drops during rapid filling of the ventricle.
d.Ventricular filling is primarily due to the pressure gradient between the left atrium and ventricle, even though the pressure differences are small.
e.During diastolic filling, atrial pressure is only slightly greater than ventricular pressure because there is little resistance to blood flow across the normal mitral valve. |
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Term
| What happens during Atrial Contraction? |
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Definition
a.initiated near the end of diastole once atrial depolarization occurs (signified by the P wave)
b.atrial contraction increases atrial pressure slightly, and increases ventricular volume by about 10 to 20% under normal conditions
c.not essential for ventricular filling under resting conditions, but becomes more important at high heart rates (when diastolic filling time is reduced)
Note: Atrial contraction only add about 10% to ventricular filling. During exercise, its important for atria to push extra blood into ventricles. |
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Term
| What happens in Isovolumic Contraction? |
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Definition
ONSET OF VENTRICULAR SYSTOLE
a.begins once an action potential passes through the AV node and initiates ventricular depolarization
b.triggered by QRS complex
c. contraction causes intraventricular pressure to rise above atrial pressure, which closes the mitral valve
d.since the aortic valve is also closed at this time, pressure rises rapidly without a change in ventricular volume |
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Term
What happens during Ejection of blood?
Also what are the 2 reasons why pressure in the Ventricles drop? |
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Definition
EJECTION: begins when ventricular pressure rises above aortic pressure, which opens the aortic valve
a. RAPID EJECTION PHASE
1. immediately after the aortic valve opens, blood rapidly enters the aorta and causes arterial pressure to rise
b. SLOW EJECTION PHASE
1.after left ventricular and aortic pressure reach a maximum (systolic pressure), the rate of ejection and both pressures decrease
2.peak systolic pressure is nearly the same in the ventricle and aorta because there is little resistance to flow in the aortic valve
3.pressure declines throughout the slow ejection phase because the force of contraction is decreasing as ventricular volume gets smaller and due to ventricular repolarization (signified by the onset of the T wave)
4.eventually intraventricular pressure falls below aortic pressure, which results in aortic valve closure
5.closure of the aortic valve causes a small dip in arterial pressure called the dicrotic notch (at ~100 mmHg)
2 reason why ventricular pressure fall:
1.Decrease in Ca++ in cell
2.Contraction and loss of volume will decrease pressure in ventricles. |
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Term
| What happens during Isovolumic Ventricular Relaxation? |
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Definition
a. This period begins with aortic valve closure (S2) when ventricular pressure falls rapidly.
b. Ventricular volume cannot change since the mitral valve is also closed.
c. S2 signals onset of diastole.
d. Calcium levels in myocytes are decreasing. |
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Term
| What is the timing of valve events in the R and L heart during Systole? |
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Definition
The normal pressures in the right and left atria are nearly the same, ~0 to 10 mm Hg (slightly higher in the left atrium).
When the QRS complex occurs resulting in ventricular depolarization, pressure rises faster in the left ventricle than in the right ventricle (since the left ventricle has a thicker wall).
Therefore, the mitral valve will close slightly before the tricuspid valve (however, normally it is not possible to hear distinct closures of each valve as they occur at nearly the same time).
As ventricular pressure continues to rise, the pulmonic valve will open at a much lower pressure (~10 to 16 mm Hg) than does the aortic valve (80 mm Hg).
Therefore, the pulmonic valve will open slightly before the aortic valve during systole.
Mnemonic: Mitral valve closure, Tricuspid Valve Closure, Pulmonic Valve Opening, Aortic Valve opening (Merrill Tarr, Potassium Always) |
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Term
| What is the Timing of events in the R and L heart during Diastole? |
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Definition
During diastole, the sequence of valve events is the opposite of that which occurs in systole:
-Aortic closure valve (A2)
-Pulmonic valve closure (P2) (these two valve closures constitute S2)
-Tricuspid valve opening
-Mitral valve opening
Aortic valve valve closure precedes pulmonic closure, and distinct clicks of these valve closures can normally be heard when a person inspires.
This is called “physiological splitting of the second heart sound”, |
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Term
| What is the difference between Arterial Diastolic Pressure versus Ventricular End Diastolic Pressure? |
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Definition
DP: arterial diastolic pressure
This is the pressure in the aorta (and systemic arteries) at the time of opening of the aortic valve. It is normally about 80 mm Hg.
Pressure in the systemic arteries continues to fall until ejection from the ventricle begins. Arterial pressure will continue to fall during the isovolumic contraction phase, so arterial diastolic pressure is reached during ventricular systole.
EDP: end diastolic pressure
This is the pressure in the ventricle at the end of diastole. It is normally very low (~0 to 10 mm Hg).
This ventricular pressure is reached at the end of ventricular filling, so it occurs at the end of diastole. |
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Term
| When are the heart sounds heard? |
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Definition
Note: Systole occurs from S1 to S2; Diastole occurs from S2 to S1
S1: the first heart sound is due to closure of the mitral and tricuspid valves (which signifies the onset of isovolumic contraction immediately after the QRS complex).
S2: the second heart sound arises from closure of the aortic and pulmonic valves at the end of ejection. It occurs near the end of the T wave and signifies the start of isovolumic relaxation.
S3: the third heart sound occurs at the onset of rapid ventricular filling and is due to vibration of the ventricular wall.
S4: the fourth heart sound occurs during atrial contraction and is due to vibration of the mitral or tricuspid valve leaflets by blood flowing into the ventricle.
S3 and S4 are not normally audible in adults. |
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Term
When are the heart sounds heard?
What is physiological splitting of S2? |
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Definition
Venous Return = flow = delta P / Resistance
1. Venous return to the right heart is a flow, and therefore is dependent on the pressure gradient (ΔP) driving the flow and the resistance (R) to blood flow:
2. If ΔP is increased (as occurs during inspiration), then venous return to the right ventricle will increase.
3. The pulmonic valve normally closes only slightly after the aortic valve does, and the interval between the two becomes wider during inspiration. During expiration, the interval between the aortic (A2) and pulmonic (P2) components of S2 is so brief that the two components of the 2nd heart sound nearly fuse. During inspiration, decreased right atrial pressure increases venous return to the right heart. Filling of the right ventricle is increased which causes a greater stroke volume on the next beat (Starling’s Law). The pulmonic valve remains open longer than normal during ejection of this greater stroke volume and so pulmonic valve closure is delayed relative to aortic valve closure on inspiration. |
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Term
| What is physiological splitting of S2? |
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Definition
On expiration, closure of the aortic valve closes only slightly before the pulmonic valve closes. As a result, a single sound is heard for S2 on expiration.
As we have seen, inspiration increases venous return to the right heart, which increases filling of the right ventricle (increased preload). In inspiration, the increased end diastolic volume in the right ventricle will result in a greater stroke volume which will delay closure of the pulmonic valve. There will be two distinct sounds for S2 in inspiration: first, due to closure of the aortic valve, followed by closure of the pulmonic valve.
This is a normal event due to the effect of breathing on venous return to the heart: inspiration causes physiological splitting of S2. |
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Term
| What is the cause of Wide Splitting of S2? |
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Definition
Wide splitting: The pulmonic valve closes after the aortic valve during expiration and inspiration (delay greater with inspiration).
Wide splitting occurs when ejection from the right ventricle is prolonged, which delays pulmonic valve closure:
1. right bundle branch block: slower depolarization of the right ventricle prolongs ejection.
2. pulmonic stenosis: the high resistance of a stiff pulmonic valve prolongs ejection from the right ventricle.
Note: Under normal conditions, splitting of S2 only occurs upon inspiration. In contrast, then ejection from the right ventricle is prolonged, splitting of S2 is heard on both inspiration and expiration. As a result, the pulmonic valve closes after the aortic valve in both inspiration and expiration, with the greatest splitting heard during inspiration. |
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Term
| What is the cause of Paradoxical Splitting of S2? |
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Definition
Paradoxical splitting: Splitting is heard upon expiration rather than inspiration (which is the reverse pattern of normal conditions), and occurs when ejection from the left ventricle is prolonged during both expiration and inspiration (which delays aortic valve closure compared to normal):
1. left bundle branch block: this conduction defect results in a longer time to depolarize the left ventricle and so a longer ejection time
2. aortic stenosis: the high resistance of the stiff valve results in prolonged ejection |
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Term
| What are the common causes of Altered Intracardiac Pressures in Right Atrial Pressure? |
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Definition
RIGHT ATRIAL PRESSURE (normal range 0 - 8 mm Hg)
A. Reduced pressure
1. Hypovolemia (low blood volume)
2. Impaired venous return to heart
B. Increased pressure
1. Tricuspid stenosis (stiff valve)
2. Right ventricular failure
3. Cardiac tamponade (pericardial sac fills with fluid and compresses the chambers of the heart) |
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Term
| What are the Common causes of altered intracardiac pressure in Right Ventricular Systolic and Diastolic Pressure? |
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Definition
INCREASED RIGHT VENTRICULAR SYSTOLIC PRESSURE (normal range 15-30 mm Hg)
A. Right ventricular hypertrophy (chronic change)
1. Pulmonic valve stenosis (stiff valve)
2. Chronic pulmonary hypertension (as in persons living at high altitude)
B. Increased contractility (acute change)
INCREASED RIGHT VENTRICULAR DIASTOLIC PRESSURE (normal 0 - 8 mm Hg)
A. Right ventricular hypertrophy
1. a thicker wall has decreased compliance If compliance is decreased, a change in volume will now produce a larger change in ventricular diastolic pressure during filling compared to normal.
B. Right heart failure (may have decreased compliance) |
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Term
| What are the Common causes of altered intracardiac pressure such as an increased in pulmonary artery pressures? |
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Definition
INCREASED PULMONARY ARTERY PRESSURES (normal systolic pressure 15 - 30 mm Hg; normal diastolic 4 -12 mm Hg)
A. Left-sided heart failure
B. Pulmonary hypertension (high altitude or acute hypoxia)
C. Mitral stenosis |
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Term
| What are the Common causes of altered intracardiac pressure in Left Ventricular Systolic and Diastolic Pressure? |
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Definition
INCREASED LEFT ATRIAL PRESSURE (normal 1 - 10 mm Hg)
A.Mitral stenosis
INCREASED LEFT VENTRICULAR SYSTOLIC PRESSURE (normal 100 -140 mm Hg)
A. Ventricular hypertrophy
B. Increased contractility
INCREASED LEFT VENTRICULAR DIASTOLIC PRESSURE (normal 3 -12 mm Hg)
A. Ventricular hypertrophy
B. Aortic valve insufficiency |
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Term
Define Pre-Load:
What determines Pre-load? |
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Definition
Preload is defined as stretch on the myocardial fibers before contraction.
Preload is related to ventricular filling.
Because stretch is difficult to measure directly, several variables related to ventricular filling have been used as indices of preload:
-End-diastolic volume (EDV)
-Venous return
-End-diastolic pressure (EDP)
Preload is determined by:
1. Filling Time (Ventricular Diastole)
A. Heart rate
2. Rate of Venous Return
A. Venous Tone
B. Blood volume
1. Reduced (hemorrhagic shock, dehydration)
2. Increased in some forms of hypertension
C. Gravity (venous pooling) |
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Term
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Definition
Afterload is defined as the ventricular wall tension during ejection. It is the resistance that must be overcome to eject blood.
Wall stress = Pressure x ventricular radius / (2 x wall thickness) (Law of LaPlace)
Pressure during ejection is the main factor determining wall stress.
Pressure at the start of ejection (aortic diastolic pressure) or peak pressure (aortic systolic pressure) are used as indices of afterload. |
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Term
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Definition
Inotropic state (or contractility) represents the force of contraction: it is dependent on the cytosolic calcium level within contracting myocytes.
Unlike skeletal muscle where cytosolic Ca++ levels are supramaximal during contraction, in the contracting ventricle cytosolic Ca++ levels are submaximal for cross-bridge activation under normal conditions.
Therefore, conditions which increase Ca++ levels in contracting myocytes will result in formation of more cross bridges and increased contractile force (increased inotropic state).
Norepinephrine (released from sympathetic nerves) will enhance calcium entry into myocytes (increased calcium current), and increase inotropic state. |
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Term
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Definition
Starling's Law of the heart states that stroke volume increases when preload is increased.
Cytosolic Ca++ during contraction is the same at any EDV along this single Starling curve.
The increased force of contraction at greater preload is due to stretch which results in more favorable overlap of thin and thick filaments.
Note: It we fill the ventricles, it will pump! If we fill the ventricles more, we get an increase stroke volume. Increasing Stroke volume by increasing pre-load is NOT related to increasing inotropic state.
At low EDV, sarcomere length is so low that few cross-bridges can be formed.
As preload increases, sarcomere length increases and this allows more cross-bridges to form during systole.
Therefore, increasing EDV allows a more optimal overlap of thin and thick filaments which allows more cross-bridges to form.
This results in a greater force of contraction and increased stroke volume (not due to increase in Ca++) |
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Term
| Movement along the Starling Curve does what? |
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Definition
Moving from point 1 to point 3 resulted in a decreased EDV and reduced SV due to either:
1. decreased venous return, or
2. decreased filling time due to increased heart rate.
Moving from point 1 to point 2 resulted in an increased EDV and greater SV due to either:
1. increased venous return, or
2. increased filling time due to decreased heart rate. |
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Term
| What is Starling’s Law on Pre-load? |
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Definition
1. Changes in venous return or filling time (i.e., heart rate) will affect stroke volume by altering end-diastolic volume.
2. Preload determines the sarcomere length, and therefore the number of cross-bridges that can potentially form during the next contraction.
3. Changes in preload shift points along a single Starling curve in either direction.
4. The intracellular calcium concentration in contracting myocytes is the same at all points along a single Starling curve.
5. Increased stroke volumes at higher end-diastolic volumes are due to more optimal filament overlap within myocytes, and not due to increased contractility. |
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Term
On a SV Vs EDV curve:
Moving from point 1 (normal) to point 2 (same line but higher SV) is due to what?
Moving from point 1(normal) to point 2 (same line but lower SV) is due to what? |
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Definition
Moving from point 1 to point 2 resulted in an increased EDV and greater SV due to either:
1. increased venous return, or
2. increased filling time due to decreased heart rate.
Moving from point 1 to point 3 resulted in a decreased EDV and reduced SV due to either:
1. decreased venous return, or
2. decreased filling time due to increased heart rate. |
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Term
| On a SV vs EDV curve, the shift from point 1 (normal) to point 3 (higher line) is due to what? And from point 1 to point 2? |
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Definition
At the same EDV, decreased afterload results in an increased SV (point 1 to point 3).
At the same EDV, increased afterload results in a decreased SV (point 1 to point 2).
Changes in systemic arterial pressure are one cause of changes in afterload. |
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Term
| What is Starling’s Law on Afterload? |
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Definition
When afterload increases, the entire Starling curve of SV versus EDV shifts downwards.
When afterload decreases, the entire Starling curve shifts upward.
The intracellular calcium concentration in contracting myocytes is the same along the normal Starling curve and those curves shifted upwards or downwards are due to altered afterload.
A way to help distinguish preload and afterload is as follows:
Preload represents ventricular filling which occurs prior to contraction (pre).
Afterload represents the force the ventricle has to overcome during ejection, so it involves factors after ventricular contraction begins. |
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Term
| What are some examples of Altered Afterload? |
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Definition
1. Increased TPR due to systemic arteriolar constriction
A. Administration of a vasoconstrictor (acute increase in afterload)
B. Some forms of hypertension (chronic increase in afterload)
2. Decreased TPR due to systemic arteriolar dilation
A. Administration of a vasodilator
B. Anaphylactic shock (ie. Is bee sting)
3. Aortic stenosis (stiff valve): increased afterload to left ventricle even though TPR is normal |
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Term
What are the effects of increasing Inotropic state vs decreasing inotropic state on a SV vs EDV curve.
What causes an increased Inotropic state and decreased Inotropic state? |
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Definition
Increased inotropic state (contractility) results in an increased SV (curve is shifted upward) even at the same preload (point 1 to point 3).
Decreased inotropic state (contractility) will reduce SV (curve is shifted downward) even at the same preload (point 1 to point 2).
2)
1. Increased Inotropy
A. Increased sympathetic nerve firing to heart
B. Administration of a beta agonist
C. Cardiac glycoside
2. Decreased Inotropy
A. Decreased sympathetic nerve firing to heart
B. Administration of a beta antagonist
C. Administration of a calcium channel blocker
D. Heart failure |
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Term
| What is Starling’s law on Inotropic state? |
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Definition
For any given preload (EDV), an increase in contractility will increase stroke volume while a decrease in contractility will decrease stroke volume.
An increase in inotropic state is seen as an upward shift in the Starling curve (SV versus EDV), while a decrease in inotropic state is seen as a downward shift in the Starling curve (SV versus EDV).
Sympathetic nerves and cardiac glycosides enhance the force of contraction (i.e., greater inotropic state, increased contractility) by increasing cytosolic calcium levels within myocytes. |
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Term
| In summary, what is Starling’s Law? |
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Definition
Changes in heart rate or venous return will shift EDV to a new point on the same Starling curve.
Changes in contractility or afterload will shift the entire Starling curve above or below the original one. |
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Term
| What is Starling Reserve, Inotropic Reserve and Total Cardiac Reserve? |
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Definition
The Starling Reserve is the maximal increase in stroke volume that can be achieved by increasing EDV.
The Inotropic Reserve represents the extent that increased contractility can raise stroke volume.
The Total Cardiac Reserve is the sum of the Inotropic and Starling Reserves. |
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Term
| What does the isovolumic curve represent? |
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Definition
The isovolumic curve represents the maximal pressure that can be developed at any ventricular volume.
Increases in EDV (preload) raise the peak isovolumic pressure, while decreases in the EDV reduce the maximal isovolumic pressure.
This effect is the same as we have discussed in regard to Starling's Law of the heart: increases in end-diastolic volume increase sarcomere length, which results in more optimal cross bridge overlap, and therefore, greater force of contraction.
This isovolumic curve is also called Po (pressure at zero ejection), or the end-systolic pressure volume relationship (ESPVR). |
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Term
What are the different pressures from PV loops?
-Ventricular End-diastolic pressure
-Peak ventricular systolic pressure
-Aortic pressures: Diastolic pressure & Systolic pressure |
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Definition
Ventricular end-diastolic pressure is the pressure at the end of filling at the time that the QRS complex occurs.
Peak ventricular systolic pressure is the maximal pressure achieved during ejection.
Aortic pressures can also be determined from this graph:
1. Diastolic pressure in the aorta is the pressure when ejection begins (since this determines the time of aortic valve opening).
2. Systolic pressure in the aorta is equal to peak ventricular systolic pressure (when the aortic valve is normal and has low resistance to flow). |
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Term
| What is the rate of ejection? If Aortic Diastolic Pressure increases, what will happen to SV? |
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Definition
The rate of ejection at the time of opening of the aortic valve is proportional to the difference between the maximal pressure which could be developed at this end-diastolic volume (the value on the Po curve) and the arterial diastolic pressure.
If afterload is increased without changing end-diastolic volume, the difference between Po and the higher arterial diastolic pressure will be decreased compared to normal, and so velocity of ejection will be reduced.
It is harder to eject blood from the ventricle when arterial blood pressure increases.
Remember that the point on the Po represents the maximal pressure possible at that EDV when there is zero ejection (so ejection velocity is zero). |
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Term
| What would increasing Preload do to SV? |
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Definition
INCREASED PRELOAD (END-DIASTOLIC VOLUME) RESULTS IN INCREASED STROKE VOLUME
This can be seen by comparing the difference in widths of the pressure-volume loops shown on the previous slide.
Systolic arterial pressure is increased compared to normal.
Aortic valve closure occurred on the same Po line compared to normal, which indicates that there is no change in contractility.
Ejection began at the same arterial diastolic pressure which indicates that there is no change in afterload.
End-systolic volume increased only slightly with the greater preload.
An acute increase in preload will increase SV in the next beat. |
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Term
| What are the effects of a decreased Preload? |
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Definition
DECREASED PRELOAD (END-DIASTOLIC VOLUME) RESULTS IN DECREASED STROKE VOLUME.
Systolic arterial pressure is decreased compared to normal.
Aortic valve closure occurred on the same Po line compared to normal, which indicates that there is no change in contractility.
Ejection began at the same arterial diastolic pressure which indicates that there is no change in afterload.
End-systolic volume decreased only slightly with the reduced preload.
An acute decrease in preload will decrease SV in the next beat.
Note: Changes in preload to the right ventricle have the same qualitative effects as shown for the left ventricular pressure-volume loops. The major difference is the lower pressures developed by the right ventricle compared to the left ventricle. |
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Term
| What are the effects of Increased Afterload? |
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Definition
INCREASED AFTERLOAD DECREASES STROKE VOLUME
The increased afterload (i.e., increased arterial diastolic pressure) can be seen by comparing the pressure where ejection begins in both PV loops.
With increased afterload, ejection begins at a higher arterial pressure compared to normal conditions.
Preload (end-diastolic volume) is the same for both PV loops.
End-systolic volume will be greater than normal since SV was decreased.
There is no difference in inotropic state since Po is the same in both conditions (i.e., aortic closure occurs on the same line).
An acute increase in afterload will reduce SV in the next beat and also reduce the rate of ejection.
An example of increased afterload is systemic arteriolar constriction following administration of a vasoconstrictor. |
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Term
| What are the effects of decreased afterload? |
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Definition
DECREASED AFTERLOAD INCREASES STROKE VOLUME
The decreased afterload (i.e., decreased arterial diastolic pressure) can be seen by comparing the pressure where ejection begins in both PV loops.
With decreased afterload, ejection begins at a lower arterial pressure compared to normal conditions.
Preload (end-diastolic volume) is the same for both PV loops.
End-systolic volume will be lower than normal since SV was increased.
There is no difference in inotropic state since Po is the same in both conditions (i.e., aortic closure occurs on the same line).
An acute decrease in afterload will increase stroke volume in the next beat and also increase the rate of ejection.
An example of decreased afterload is systemic arteriolar dilation following administration of a vasodilator or development of anaphylactic shock. |
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Term
| What are the effects of an Increased in Inotropic State? |
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Definition
Increased inotropic state is seen as a shift in the Po curve to the left (without an upward shift in the diastolic filling curve).
Preload (EDV) and afterload (arterial pressure at the time of aortic valve opening) are the same for both pressure-volume loops.
Increased contractility resulted in a greater SV (and lower end-systolic volume) as well as an increased arterial systolic pressure.
Ejection fraction is increased with increased contractility (SV is increased even though EDV did not change).
Increased contractility can result from increased sympathetic tone to the heart. Norepinephrine increases calcium current, which elevates cytoplasmic calcium levels during systole, resulting in more cross-bridge formation, and consequently more force.
Examples of increased inotropic state are increased sympathetic nerve firing to the heart or administration of a beta agonist. |
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Term
| What are the effects of decreased Inotropic State? |
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Definition
Decreased inotropic state is seen as a shift in the Po curve to the right.
Preload (EDV) and afterload (arterial pressure at the time of aortic valve opening) are the same for both pressure-volume loops.
Decreased inotropic state resulted in a reduced SV (and greater end-systolic volume) as well as an decreased arterial systolic pressure.
Ejection fraction is decreased with decreased contractility (SV is decreased at the same EDV).
Examples of decreased inotropic state are reduced sympathetic nerve firing to the heart or administration of a beta antagonist. |
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Term
| What does the curve in Ventricular hypertrophy look like? |
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Definition
Ventricular hypertrophy results in more sarcomeres within larger myocytes, and so increased force can be generated. This is shown above by the leftward shift in the Po curve.
The increased force due to hypertrophy (increased size of myocytes, more cross-bridges) is due to a different mechanism than the increased force due to increased inotropic state (increased cytosolic calcium levels).
The second effect of the hypertrophy is a decrease in ventricular diastolic compliance (distensibility). During filling, ventricular pressure will be higher in a hypertrophied heart than a normal heart at any EDV, which impairs filling. This is depicted in the resting or diastolic pressure-volume curve being rotated upwards and to the left.
This decrease in compliance results in higher end-diastolic pressures in the hypertrophied heart compared to the normal heart.
Note: The Po curve is shifted to the left in this example, but it is not due to increased inotropic force.
The diastolic filling curve is shifted up compared to normal.
The increased force is due to ventricular hypertrophy.
Also:
The hypertrophied ventricle can generate greater force due to increased muscle mass (left shift in the Po curve compared to normal).
Left ventricular diastolic pressure (LVEDP) will be elevated by left ventricular hypertrophy due to decreased compliance.
The rise in LVEDP increases upstream pressures (increased left atrial pressure, pulmonary venous pressure, pulmonary capillary pressure, and cause pulmonary edema).
The increase in the upstream pressures will be:
a. greatest in the left atrium and slightly less in each adjacent segment
b. dependent on the degree of ventricular hypertrophy
A chronic rise in left atrial pressure can lead to atrial hypertrophy (seen as an enlarged P wave).
Left ventricular hypertrophy can cause a left axis shift of the mean electrical axis for ventricular depolarization. |
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Term
| What is the equation for Compliance? |
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Definition
Compliance = delta V / delta P
So increased P = decreased V |
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Term
| What does Systolic vs Diastolic Dysfunction look like? |
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Definition
In heart failure, systolic dysfunction can develop as seen by a rightward shift in Po curve. As a result, the ventricle is able to develop less force and pressures are reduced.
Diastolic function can also develop in heart failure and is seen as an upward shift in the diastolic filling curve. As a result, it is harder to fill the ventricle and ventricular end-diastolic pressure is increased.
Either systolic or diastolic dysfunction or both can develop in heart failure.
Stroke work (the area of the pressure-volume loop) is markedly reduced when systolic and diastolic dysfunction develops. |
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Term
What is the Direct Fick Method for measuring Cardiac Output?
2) What is the equation for Cardiac Output for this example? |
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Definition
The gold standard for measuring cardiac output is the direct Fick method.
The Fick equation states that the amount of blood flowing through the systemic circulation (cardiac output) is equal to the rate of oxygen (O2) consumption by the systemic organs divided by the difference in O2 contents of systemic arterial and venous blood.
2)
CARDIAC OUTPUT = O2 Consumption by Systemic Organs / (Systemic Artery O2 Content - Systemic Vein O2 Content)
It is difficult to directly measure O2 consumption by systemic organs. |
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Term
| Oxygen can be measured how? Under steady-state conditions, what happens to oxygen uptake? |
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Definition
Oxygen uptake from the lungs can be measured using a spirometer.
Oxygen consumption by systemic organs is more difficult to measure than oxygen uptake across the lungs.
Under steady-state conditions, however, oxygen uptake is equal to oxygen consumption.
If there is no shunt:
1. O2 content in systemic venous blood is equal to that of pulmonary arterial blood.
2. O2 content in systemic arterial blood is equal to that of pulmonary venous blood. |
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Term
| What is the indirect Fick Method to measure Cardiac Output? |
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Definition
There are several indirect Fick methods for measuring cardiac output, one of which is the thermal dilution technique.
A multilumen catheter containing a thermocouple (which measures blood temperature) is inserted into a vein, and advanced until the catheter is positioned within the pulmonary artery.
Cold saline is injected through a hole in the catheter upstream from the thermocouple.
The thermocouple measures the change in blood temperature resulting from injection of the cold saline.
The thermal dilution technique is frequently used in the intensive care setting to monitor a patient's cardiac output over time.
PBF (ml/min) = [60 x K x Vi x (Tb-Ti)] /A
PBF = pulmonary Blood flow |
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Term
| What is the Normal Oxygen Contents? |
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Definition
The O2 content in systemic venous blood returning to the right atrium is about 15 ml O2 per 100 ml of blood. This O2 content does not change until O2 diffuses into pulmonary capillaries, raising the O2 content to about 20 ml O2 per 100 ml of blood.
Under normal conditions, there are two different O2 contents within the cardiovascular system: deoxygenated blood (~15 ml O2/100 ml blood) and oxygenated blood (~20 ml O2/100 ml blood). If there is an intracardiac shunt, there will be three different O2 contents within the cardiovascular system. |
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Term
| What happens to Cardiac Output in Intracardiac Shunts? |
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Definition
In the absence of a cardiac shunt:
-cardiac output is equal to pulmonary blood flow.
If there is an intracardiac shunt:
-the magnitude of the shunt is equal to the difference between pulmonary blood flow and cardiac output. |
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Term
| What are the two important changes that signify the presence of a shunt? |
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Definition
1. Altered blood O2 content: an abnormal change in blood O2 content of a chamber of the heart (or a vessel) compared to that in the preceding chamber (or vessel).
A. the area where the abnormal O2 level is first observed receives the shunt
B. blood O2 content is not changed in the area where the shunt originates
2. Changes in blood volume:
A. blood volume will be reduced in the area where the shunt originates
B. blood volume will be increased in the area receiving the shunt |
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Term
| What happens to shunting in Ventricular Septal Defect? |
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Definition
A ventricular septal defect (VSD) is an abnormal opening in the ventricular septum.
The shunting of blood from the left ventricle across the VSD will raise O2 content and blood volume in the right ventricle. The HALLMARK of a VSD is increased O2 content in the right ventricle compared to that of the right atrium.
Because systolic pressure is greater in the left than the right ventricle, the net direction of the shunt will always be from the left to right ventricle.
The shunt of oxygenated blood to the right ventricle will increase blood O2 content in the right ventricle above that in the right atrium.
Blood O2 content in the left ventricle will not be changed.
There is one pathway for ejection of blood from the right ventricle: into the pulmonary artery. There are two pathways for ejection of blood from the left ventricle: into the aorta and across the septal defect into the right ventricle.
Stroke volume of right ventricle will be greater than stroke volume of left ventricle:
SV from right ventricle = SV from left ventricle + volume of blood shunted
Assume that it would be possible to suddenly create a ventricular septal defect in a normal person in one beat.
After creation of the ventricular septal defect, pulmonary blood flow would be greater than normal due to the shunting of blood from the left ventricle to the right ventricle.
Cardiac output would be decreased compared to normal, and this would decrease mean arterial pressure.
Decreased mean arterial pressure would initiate reflex responses to restore arterial pressure towards normal.
One response would be to increase angiotensin II formation (ANG II). |
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Term
| What are the effects of Increasing Angiotension II levels following decreased Mean Arterial Pressure? |
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Definition
Decreased MAP results in increased renin release from the kidney, which increases circulating levels of ANG II.
ANG II is a potent vasoconstrictor and also increases aldosterone release from the adrenal gland.
Aldosterone promotes reabsorbtion of sodium and water from the kidney, which will increase blood volume (and therefore increase cardiac output). Ultimately, increasing MAP towards normal. |
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Term
| What is the outcome in a person with VSD? |
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Definition
Total blood volume will be increased compared to normal in a person with a ventricular septal defect.
Blood volume will increase via increased circulating aldosterone until cardiac output is sufficiently increased to restore mean arterial pressure to normal values.
A ventricular septal defect will result in an additional circuit for the flow of blood.
Blood volume will be greater than normal in a person with a ventricular septal defect.
This allows systemic cardiac output to remain within normal values.
As a result, blood volume will be increased in all chambers of the shunt pathway (left ventricle, right ventricle, pulmonary circulation, and left atrium).
Over time, the increased volumes will result in HYPERTROPHY of the right and left ventricles as well as the left atrium.
The additional circuit for flow of blood due to the shunt is shown in red. |
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Term
| What happens to shunting in Atrial septal Defect? (ASD) |
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Definition
An atrial septal defect (ASD) is an opening in the septum between the left and right atria.
The shunting of blood from the left atrium across the ASD will raise O2 content and blood volume in the right atrium. The HALLMARK of an ASD is increased O2 content in the right atrium compared to that of the systemic veins.
Normally the direction of the shunt across an atrial septal defect is from the left atrium to the right atrium (since pressures are usually slightly higher on the left side).
The introduction of oxygenated blood into the right atrium increases its blood O2 content and volume compared to normal.
End diastolic volume of the right ventricle will be increased by the amount of blood shunted, and right ventricular stroke volume will be increased.
End diastolic volume and stroke volume will be greater in the right ventricle than in the left ventricle.
Blood volume will increase in order to maintain cardiac output to systemic organs within normal limits in spite of the shunting.
As a result, blood volume within the left atrium, right atrium, and right ventricle will be greater than normal. Over time, the increased volumes will result in HYPERTROPHY of these chambers. |
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Term
| How does shunting in Ductus Arteriosus work? |
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Definition
The ductus arteriosis is an opening between the pulmonary artery and the aorta.
In utero, the lungs of the fetus are not inflated. As a result, O2 levels in the lung are very low. Low O2 levels cause pulmonary arterioles to constrict, which increases pulmonary vascular resistance and pulmonary artery pressure.
The high pulmonary vascular resistance in utero results in very low pulmonary blood flow. Instead, most of the blood ejected from the right ventricle crosses the ductus arteriosus into the aorta, where it flows to systemic organs.
How will the MEA of a newborn compare to that of a healthy adult? |
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Term
| How will the MEA of a newborn compare to that of a healthy adult? |
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Definition
| The high pressure in the pulmonary artery in utero will result in right ventricular hypertrophy, and infants will have a right axis deviation of the MEA immediately after birth. Once pressure in the pulmonary artery decreases at birth upon inflation of the lungs, the hypertrophy of the right ventricle will slowly reverse over the next few months and the MEA will eventually be in the normal range. |
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Term
| What happens in Patent Ductus Arteriosus? What does Patent mean? |
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Definition
Patent means prolonged/extended.
The shunting of blood from the aorta across the PDA will raise O2 content and blood volume in the pulmonary artery. The hallmark of a PDA is increased O2 content in the pulmonary artery compared to that of the right ventricle. |
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Term
| What happens if we have a failure of the ductus arteriosus to close after birth? |
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Definition
Normally the ductus arteriosus closes after birth in response to the higher O2 levels following inflation of the lungs. The higher O2 levels in the lung cause pulmonary arterioles to dilate, which lowers pulmonary vascular resistance. This decreases pulmonary artery pressure, and the higher pressure in the aorta closes the ductus arteriosus.
Failure of the ductus arteriosus to close results in blood shunted from the aorta to the pulmonary artery (since pressure is higher in the aorta).
On each beat, the left ventricle is filling with the amount of blood ejected by the right ventricle plus the blood shunted across the ductus arteriosus (since it flows through the pulmonary circulation, the left atrium, and back to the left ventricle). Therefore, end diastolic volume in the left ventricle will be greater than in the right ventricle.
During systole, the amount of blood ejected from the left ventricle will be greater than the right ventricular stroke volume (due to increased end diastolic volume).
Not all of the blood ejected by the left ventricle will reach the systemic organs as some is shunted from the aorta to the pulmonary artery. |
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Term
| Where does hypertrophy occur in PDA? |
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Definition
Blood volume will increase in order to maintain sufficient cardiac output to systemic organs in spite of the shunt.
As a result, blood volume will be chronically increased within the pulmonary circulation, left atrium, and left ventricle, resulting in hypertrophy of these cardiac chambers.
If the shunt is very large, pulmonary arterial pressure can increase so much that right ventricular hypertrophy occurs.
The additional circuit for flow of blood due to the shunt is shown in red. |
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Term
| In what chambers would abnormal O2 content first appear in VSD, ASD, and Patent Ductus Arteriosus? |
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Definition
VSD – Right Ventricle
ASD – Right Atrium
PDA – Pulmonary Artery |
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Term
What is the equation for MAP?
Arterial pressure is dependent on what? |
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Definition
MAP = Diastolic Pressure + 1/3 Pulse Pressure
MAP = Diastolic Pressure + 1/3 (Systolic Pressure - Diastolic Pressure)
Arterial pressure is dependent on the volume of blood within the arterial system:
Rate of inflow to arterial system vs Rate of runoff to veins
Arterial pressure rises when inflow is greater than outflow (during the rapid ejection phase of ventricular systole).
Arterial pressure falls when inflow is less than outflow (during diastole). |
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Term
| What are the determinants of Arterial Diastolic Pressure? |
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Definition
DIASTOLIC PRESSURE: determined by factors that alter either the rate or time of runoff:
1. Rate of runoff: how fast blood flows from the arterial system to the venous system.
2. Runoff time: runoff occurs during diastole (while the ventricle is filling) |
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Term
What is the rate of Runoff and Diastolic Pressure and what does it depend on?
What is the major determinant of runoff time? |
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Definition
1)
Runoff is the flow of blood from the arterial system to the venous system. This flow is dependent on the systemic arteriolar resistance:
1. Systemic arteriolar dilation (decreased TPR) results in a lower resistance to flow and so a higher rate of runoff, which lowers arterial diastolic pressure.
2. Systemic arteriolar constriction (increased TPR) results in a higher resistance and so a lower rate of runoff, which raises arterial diastolic pressure.
2)
The major determinant of runoff time is heart rate). The length of diastole decreases as heart rate increases:
1. Decreasing heart rate increases runoff time, so arterial diastolic pressure will decrease.
2. Increasing heart rate decreases runoff time, so arterial diastolic pressure will increase. |
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Term
| What are the determinants of Systolic Pressure? |
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Definition
1. Ejection rate:
A. The rate of ejection from the left ventricle determines how quickly blood volume in the arterial system increases, which influences the peak systolic pressure attained.
B. In aortic stenosis, arterial pulse pressure is reduced because the rate of ejection of blood is decreased due to the high resistance of the aortic valve.
2. Stroke volume:
A. The rise in arterial pressure during ejection is directly proportional to the volume of blood added to the arterial system (stroke volume).
Pulse pressure (systolic – diastolic pressure) is directly proportional to stroke volume.
If stroke volume increases (from the same arterial diastolic pressure), arterial systolic pressure will be increased.
3. Arterial compliance:
A. Chronic decreases in compliance associated with aging raise arterial systolic pressure. |
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Term
What is compliance?
What is the equation for compliance?
Decrease arterial compliance is due to what? |
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Definition
The distensibility of the arteries allows their diameter to increase slightly during ejection, which minimizes the rise in arterial systolic blood pressure. Compliance is defined as ∆volume/ ∆pressure.
Decreased arterial compliance occurs with aging resulting in an increased arterial systolic pressure (even though stroke volume remains normal).
Compliance of arterial system = Δ Volume / Δ Pressure = Stroke Volume / Pulse Pressure
Aging results in a decreased arterial compliance:
decrease Compliance = Δ Volume / change in pressure = Stroke Volume / increase in pulse pressure |
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Term
| What happens in Arteriosclerosis? |
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Definition
With aging, arterial compliance is reduced which results in a greater increase in arterial pressure during ejection compared to a younger person.
As a result, an older person with arteriosclerosis (i.e., hardening of the arteries) will have a higher arterial systolic pressure than that of a younger person during ejection of the same stroke volume.
In an older person, decreased arterial compliance will reduce elastic recoil during diastole. This will result in a faster decrease in arterial pressure during diastole and a lower arterial diastolic pressure than seen in a younger person. |
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Term
1)What is the major resistance of TPR?
2)Which has the lowest velocity of blood flow? Why? |
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Definition
1) Arteriolar resistance is the major component of TPR.
2) Capillaries have the lowest velocity of blood flow among systemic vessels
Note: If blood flow is the same through vessels of different sizes, the velocity of flow is inversely proportional to the cross-sectional area of the vessel.
The reason that the velocity of blood flow is lowest in capillaries is that their total cross sectional area is greater than any other vessel segment. |
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Term
| What is the vessel compliance difference between arteries and arterioles as oppose to venules and veins? |
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Definition
Arteries and arterioles have low compliance due to their thick muscular walls. A relatively small increase in the blood volume within the arterial system will increase arterial pressure significantly.
In contrast, venules and veins are highly compliant in relation to the arteries. Large increases in venous blood volume produce a relatively small increase in venous pressure.
In addition, increased firing of sympathetic nerves to veins causes venoconstriction, which stiffens the wall and decreases venous compliance, resulting in increased venous pressure.
Note: in veins, decrease compliance will lead to an increase in venous pressure, and an increase in blood back to the atrium. |
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Term
| How does Venoconstriction affect venous return? |
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Definition
Venoconstriction does not significantly reduce the radius of veins, so there is little change in venous resistance. Because of the large diameter of veins, venous resistance to blood flow is extremely low.
Venoconstriction decreases venous compliance, which causes the pressure within veins to increase which increases the pressure difference between peripheral veins and the right atrium.
The increased pressure gradient increases venous return to the heart.
Therefore, venoconstriction results in increased pressure within peripheral veins without a change in venular resistance, resulting in increased venous return to the heart. |
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Term
What is the equation for Flow through Tubes?
Which tubes with difference resistance will have the highest flow? |
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Definition
Flow = change in pressure / Resistance.
The tube with the lowest resistance will have the highest flow.
The tube with the highest resistance will have the lowest flow |
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Term
What is Total Peripheral Resistance?
What is the equation for TPR? |
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Definition
TOTAL PERIPHERAL RESISTANCE (TPR) (also called systemic vascular resistance, or SVR) is the sum of all resistances to flow from all vessel segments.
It represents the vascular resistance from the aorta to the right atrium (remember that the ARTERIOLES are the site of the GREATEST vascular resistance).
CO = (MAP – RAP)/TPR so…. TPR = (MAP-RAP)/CO
Unit is dyne sec/cm^5 |
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Term
| What is the difference between Series Resistances vs Parallel Resistances |
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Definition
Since the vessel segments are arranged in SERIES, the total peripheral resistance is equal to the sum of the resistances of all vessels:
TPR = Rarteries + Rarterioles + Rcapillaries + Rvenules + Rveins
Adding additional resistance (R5) in series will increase total resistance:
Series are not well put together because if organs were set in series, then the later/last organs would receive the lowest O2 content
Since the systemic organs are arranged in PARALLEL, the sum of the inverse of the vascular resistance of each organ equals the inverse of the total peripheral resistance.
One implication of this relationship is that TPR will be lower than the lowest organ vascular resistance.
Adding additional resistance (R5) in parallel will decrease total resistance:
1/Rinitial = 1/R1 + 1/R2 + 1/R3 + 1/R4
1/Rfinal = 1/R1 + 1/R2 + 1/R3 + 1/R4 + 1/R5
Rfinal < Rinitial |
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Term
What is Poiseulle’s Law?
What is blood viscosity? |
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Definition
Poiseulle’s Law describes the determinants of flow through a tube. In this equation: F = flow (ml/sec), P = Pressure, and R = Resistance. The principal determinants of resistance are: η = viscosity, L = length of tube, and r = the radius of the vessel.
Resistance (R) is inversely proportional to the vessel radius to the fourth power. To illustrate, a 16% decrease in the radius (i.e., from 1 to 0.84) doubles the resistance. If the pressure difference (ΔP) remains the same, this 16% decrease in vessel radius reduces blood flow by 50%.
Changes in the radius of arterioles are the major influence on TPR.
Resistance to blood flow is directly related to the viscosity (η) of the blood, which is largely determined by the erythrocyte concentration (i.e, hematocrit). |
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Term
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Definition
| In people living at high altitude, the physiological response to the lower blood oxygen content is an increased production of red blood cells, resulting in increased blood viscosity and therefore, greater resistance to blood flow. |
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Term
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Definition
The probability of turbulent flow is greater if flow increases, viscosity decreases (i.e., decreased hematocrit), or the vessel radius decreases.
Resistance to flow is much greater with turbulent than laminar blood flow.
Turbulent blood flow causes vibrations of the blood vessel wall which are transmitted through the tissue and can be heard with a stethoscope. These sounds are called bruits. |
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Term
| What is the effect of Gravity on Blood pressures? |
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Definition
Upon standing, the pressure in the veins below the heart increases while venous pressure decreases above the heart. The magnitude of the change in blood pressure at any point in the circulation equals the vertical distance (in cm) at that point from the level of the heart multiplied by the density of blood (~1.06). The unit of pressure is cm H2O. However, since blood pressures are usually expressed in mm Hg, the pressure in cm H2O is divided by 1.36. Since arterial blood will also be affected by gravity, arterial pressures above and below the heart change by the same amount as venous pressures.
Pressure is highest in your feet when standing up. There will be an increase in venous pressure, increase in capillary pressure, increase filtration, and feet swells |
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Term
| What is the venous pooling upon standing? |
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Definition
Because veins are highly compliant vessels, the increase in venous pressure upon standing causes the veins to distend (which minimizes the increase in venous pressure).
As a result, blood pools within peripheral veins in the legs (the volume of blood in veins increases).
Venous return to the right heart will decrease upon standing, which will reduce end diastolic volume, decrease stroke volume (Starling’s Law), and so reduce cardiac output. |
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Term
| How does the blood traveling up the veins heading to your right heart prevent itself from going backwards? |
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Definition
| The veins in the legs contain one-way valves which direct blood toward the right heart. Contraction of skeletal muscles compresses veins in the legs, which forces blood toward the heart. When the skeletal muscles relax, the venous valves prevent the backward flow of blood. |
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Term
| When you inspire, what happens in the Right ventricle vs the Left ventricle? |
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Definition
Respiratory Pump: Right Ventricle
When you inspire, you:
-increase intrathoracic volume,
-decrease intrathoracic pressure,
- decrease Right atrial pressure
-increase pressure gradient between peripheral veins and right atrium
-increase blood flow to right atrium
-increase EDV of Right atrium
-Increase Stroke Volume (leading to physiological splitting of S2)
-increase ejection time
-delayed closure of the pulmonic valve (splitting of S2)
The effect of inspiration to increase venous return to the right heart is the basis of physiological splitting of the second heart sound
The opposite effects occur on expiration.
Respiratory Pump: Left ventricle
When you inspire, you:
-increase intrathoracic volume
-decrease intrathoracic pressure
-distension of pulmonary veins
-decrease in pressure in pulmonary veins
-pooling of blood in pulmonary veins
-decrease blood flow to Left atrium
-decreased EDV of Left ventricle
-decrease Stroke Volume |
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Term
What does Expiration do?
What is the summary of Inspiration and Expiration? |
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Definition
Right Ventricle: Expiration results in opposite changes seen with inspiration:
-decreased intrathoracic volume,
-increased intrathoracic pressure,
- increased right atrial pressure,
-which decreases the pressure gradient for venous return from peripheral veins to the right heart.
-Therefore, expiration decreases filling of the right ventricle
- (decreased end diastolic volume),
-and decreased right ventricular stroke volume.
Left Ventricle:
In contrast,
-expiration increases filling of the left heart due to increase pressure of pulmonary veins
-more blood is pushed into the Left Atrium
-Increase EDV
- resulting in increased left ventricular Stroke Volume. |
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Term
What is the summary of Inspiration and Expiration?
What is a mnemonic to remember this? |
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Definition
Summary:
When you inspire:
Right Ventricle – increase EDV, increase SV
Left Ventricle – Decrease EDV, decrease SV
When you Expire:
Right Ventricle – decrease EDV, decrease SV
Left Ventricle – increase EDV, increase SV
Inspiration increases venous return to the right heart.
Expiration increases venous return to the left heart.
Inspiration Increases Venous return to the rIght Heart
Expiration increases venous return to the lEft Heart |
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Term
What is the rules for Venous return and Cardiac return ?
Where is the steady state? |
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Definition
As central venous pressure (pressure in atrium) rises, venous return to the heart decreases since the ΔP driving flow will decrease.
Under normal conditions, as central venous pressure (i.e., right atrial pressure) increases, ventricular filling is increased and cardiac output increases (Starling’s Law of the heart).
Central venous pressure will be the point where the venous function and cardiac function curves intersect. This will be the equilibrium (steady state) point where venous return will equal cardiac output. |
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Term
| Decrease and Increase in blood volume would shift the venous return and Cardiac function in what way? |
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Definition
A decrease in blood volume will shift the venous function curve downward and venous return will be decreased. Example would be hypovolemic shock.
An increase in blood volume will shift the venous function curve upwards and venous return will be increased.
A decrease in blood volume will shift the cardiac function curve downward and cardiac output will be decreased.
An increase in blood volume will shift the cardiac output curve upwards and cardiac output will be increased.
Ultimately:
A decrease in blood volume will decrease venous return and cardiac output compared to normal (shifting steady state downward)
While in increase in blood volume will increase venous return and cardiac output (shifting it upward) |
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Term
| Where are the best locations to hear cardiac valve murmurs? |
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Definition
Aortic Area
Pulmonic Area
Tricuspid Area
Mitral Area
The diagram above shows the optimal locations for hearing specific murmurs. Mitral and tricuspid valve murmurs are best heard in the apical region with the tricuspid valve adjacent to the sternum and the mitral valve more lateral. Aortic and pulmonic valve murmurs are heard best at the level of the 2nd or 3rd intercostal space, with the aortic valve on the right side of the sternum and the pulmonic valve on the left side of the sternum. |
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Term
| What are the 4 classifications of Murmurs? |
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Definition
The sound or intensity of a murmur is characterized as:
1. decrescendo: loud at the beginning and decreases in intensity
2. crescendo-decrescendo: low volume at the onset, increases in intensity, and then decreases in intensity (also called a "diamond shaped" murmur).
3. decrescendo-crescendo: loud at the beginning and decreases in intensity, then increases in intensity again near end of murmur
4. holo (also called pan): relatively constant loudness |
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Term
How are murmurs classified?
What is a mnemonic that u can use? |
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Definition
Murmurs are categorized as a:
1.systolic murmur: begins with or after the first heart sound and ends at or before the second heart sound (S1 to S2).
-Aortic Stenosis
-Mitral Regurgitation
2. diastolic murmur: begins with or after the second heart sound and ends before the first heart sound (S2 to S1).
-Aortic Regurgitation
-Mitral Stenosis
(H)ARD - Aortic Regurgitation - Diastolic
ASS – Aortic Stenosis – Systolic
MSD – Mitral Stenosis – Diastolic
MRS – Mitral Regurgitation – Systolic
The first two letters in the mnemonic define the valve defect (skip the “H” in “HARD”. The last letter in the mnemonic defines when the murmur is heard, either in systole or diastole. |
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Term
| What does the intensity of a murmur tell us? |
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Definition
The intensity of the murmur is directly related to the magnitude of the flow across the defective valve, which is dependent on the pressure gradient across the valve driving flow.
In the example of aortic stenosis above, the intensity of the murmur is dependent on ΔP across the valve, which is PLV – Paorta.
Note: if Murmur is loudest, that means that flow has increased.
Flow = change in pressure/ Resistance |
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Term
What is happening in Aortic Stenosis? (Hardening of Aortic Valve)
What is the intensity in this valve defect? |
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Definition
The aortic valve leaflets do not open completely (stiff valve), which reduces the size of the opening through which blood is ejected (increased resistance to flow).
The stenotic aortic valve increases the resistance to left ventricular ejection (greater afterload), even though total peripheral resistance is not changed.
Valve Defect:
The murmur is dependent on the pressure difference across the aortic valve:
Left ventricular pressure - Aortic pressure
The murmur begins upon aortic valve opening and continues throughout ventricular systole (until aortic valve closure, S2).
The pressure difference across the stenotic aortic valve is initially low as ejection begins, and rises as ventricular pressure increases above aortic pressure until it reaches a peak at the midpoint of ventricular systole. As ventricular pressure falls during the slow ejection phase, the pressure difference across the valve then decreases until aortic closure occurs.
This results in a systolic crescendo-decrescendo murmur. (soft-loud-soft) |
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Term
| What about the arterial pressure as a result of Aortic Stenosis? |
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Definition
Arterial Pressure:
Because of the high resistance to ejection in the stenotic aortic valve, the rate of ejection of blood is decreased.
As a result, aortic pressure rises more slowly than normal and the pulse pressure is reduced.
The time for left ventricular systole will be prolonged (while the time for left ventricular diastole is shortened). This causes paradoxical splitting of S2.
A hallmark of aortic stenosis is a large pressure difference between the left ventricle and aorta during ventricular systole. |
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Term
| What are the chronic changes in Aortic Stenosis? |
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Definition
The increased afterload due to high resistance of the stenotic aortic valve will lead to left ventricular hypertrophy over time (left axis deviation).
The Po line will shift upward and to the left due to the hypertrophy, and the diastolic filling curve will shift upwards due to decreased compliance of the ventricle.
Left atrial pressures will be increased due to decreased ventricular compliance, which may result in atrial hypertrophy.
Aortic stenosis may severely restrict increases in cardiac output (i.e., exercise).
In Aortic stenosis – even though there is a decrease in TPR, you won’t get an increase in CO because the valve is harder. |
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Term
What is another name for Aortic Regurgitation?
What is Aortic Insufficiency? |
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Definition
Regurgitation = Insufficiency
Aortic Insufficiency (regurgitation) occurs when the aortic valve leaflets fail to close completely.
The murmur begins upon incomplete closure of the aortic valve (S2).
Backflow of blood occurs from the aorta to the left ventricle during ventricular diastole. |
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Term
| What is the consequences of Backflow from Aorta to Left ventricle in Aortic Regurgitation/Insufficiency? |
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Definition
The backflow of blood across the incompetent aortic valve will result in an abnormal route of:
1. filling of the left ventricle (with acute and chronic effects)
2. runoff of blood from the arterial system. |
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Term
| What is the intensity of the Murmur in Aortic Insufficiency? |
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Definition
Dependent on the pressure difference across the aortic valve:
= Aortic pressure - Left ventricular pressure
This pressure difference decreases throughout diastole as aortic pressure decreases and left ventricular pressure increases (due to filling).
This results in a diastolic decrescendo murmur. (loud-soft) |
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Term
| What is the arterial pressures in Aortic Insufficiency? |
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Definition
A key feature of aortic insufficiency is low diastolic pressure.
Because of the backflow of blood from the aorta to the left ventricle, blood volume in the arterial system decreases faster than normal during diastole, even though total peripheral resistance (TPR) is unchanged (and so the rate of venous runoff is unchanged).
Also:
Pulse pressure is increased in aortic insufficiency.
Left ventricular end diastolic volume (LVEDV) is increased since ventricular filling now results from two routes: from the left atrium as well as backflow from the aorta.
The increase in LVEDV above normal is equal to the amount of the regurgitation.
The greater LVEDV will increase stroke volume (SV) compared to normal, and this will produce a larger pulse pressure and higher arterial systolic pressure. |
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Term
| How is Stroke Volume affected in Aortic Insufficiency? |
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Definition
The amount of blood ejected from the left ventricle during systole will be greater than that in the right ventricle (stroke volumes during systole are different between ventricles).
However, not all of the blood ejected from the left ventricle reaches systemic organs as some blood flows backwards into the left ventricle.
The "effective" left ventricular stroke volume (which is the volume which flows to the systemic organs) is less than its systolic stroke volume. |
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Term
| What are the chronic changes in Aortic Insufficiency? |
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Definition
Chronic overfilling of the ventricle results in left ventricular hypertrophy which will lead to left axis deviation.
The hypertrophied ventricle can generate greater force due to increased muscle mass (left shift in the Po curve compared to normal).
Hypertrophy results in decreased compliance of the left ventricular wall so the left ventricular diastolic filling curve will be shifted upwards.
As a result, left ventricular EDP will be increased and causing pressures upstream to increase:
-increased left atrial pressure,
- pulmonary venous pressure,
-pulmonary capillary pressure,
-and cause pulmonary edema.
A chronic rise in left atrial pressure can lead to atrial hypertrophy (seen as an enlarged P wave). |
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Term
| What is Mitral Valve Insufficiency? |
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Definition
Mitral Valve Insufficiency is Regurgitation of Mitral Valve (MRS) during systole.
Mitral insufficiency is failure of the mitral valve leaflets to close completely.
During ventricular systole, blood is pumped in two directions: into the aorta and backwards into the left atrium.
Systolic murmur |
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Term
| What is the Intensity of the Murmur in Mitral Insufficiency? |
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Definition
Dependent on the pressure difference across the mitral valve:
= Left ventricular pressure - Left atrial pressure
Because of the high ventricular pressure, the pressure difference remains relatively large throughout systole (although left atrial pressure rises markedly).
The murmur remains loud and constant throughout systole (holosystolic murmur).
Left atrial pressure will be markedly increased due to backflow across the incompetent mitral valve. |
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Term
| What are the chronic changes in Mitral Insufficiency? |
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Definition
The elevated atrial pressure can result in hypertrophy of the left atrium (seen as an enlarged P wave).
Left ventricular hypertrophy can result from a chronic elevation in left ventricular volume. |
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Term
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Definition
-Hardening of the mitral valve
The mitral valve leaflets do not open completely (stiff valve).
The murmur occurs in ventricular diastole.
The stenotic mitral valve increases the resistance to blood flow into the left ventricle. |
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Term
| What is the intensity of the murmur in Mitral Stenosis? (MSD) |
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Definition
Dependent on the pressure difference across the mitral valve:
= Left atrial pressure - Left ventricular pressure
This pressure gradient is highest at the beginning of rapid ventricular filling. As blood enters the ventricle, left atrial pressure falls during diastole.
The progressive fall in the pressure gradient across the mitral valve produces a diastolic decrescendo murmur. When atrial contraction occurs, left atrial pressure rises and the pressure gradient is increased, resulting in a presystolic crescendo murmur.
(Loud-Soft) then… (slightly soft to loud)
Decrescendo with a pre-systolic crescendo |
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Term
| What are the chronic changes in Mitral Stenosis? |
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Definition
In mitral stenosis, left atrial pressure is markedly elevated throughout the entire cardiac cycle.
The high left atrial pressure results in higher pressures upstream:
-increased pulmonary venous pressure,
-and increased pulmonary capillary pressure
-which promotes filtration in the lung,
-and pulmonary edema.
Pulmonary edema impairs O2 transport and reduces O2 levels in lung tissue.
Hypoxia causes pulmonary arterioles to constrict, which raises pulmonary vascular resistance and increases pulmonary arterial pressure.
A chronic increase in pulmonary artery pressure will result in right ventricular hypertrophy and right axis shift.
People with this valve dysfunction have a limited ability to increase cardiac output (which may limit physical activity).
The elevated atrial pressure can result in hypertrophy of the left atrium (seen as a notched P wave).
Mitral stenosis cannot result in left ventricular hypertrophy since ventricular filling is impaired. |
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Term
| What are some characteristics of Valve dysfunctions in the Right Heart? |
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Definition
The characteristics of right heart valve dysfunction are the same as for the corresponding valve in the left heart.
For example, both pulmonic and aortic stenosis will produce a crescendo-decrescendo murmur.
The location of the valve dysfunction (right vs left heart) can be determined by examining:
A. where PRESSURE CHANGES OCCUR (i.e., right atrial pressure will be increased with tricuspid stenosis)
B. AXIS SHIFTS (i.e., pulmonic stenosis will cause right axis deviation)
C. whether the murmur gets LOUDER during INSPIRATION (right side valve defect) or EXPIRATION (left side valve defect) |
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Term
| What is a Mnemonic for Cardiac Valve Defect Sound? |
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Definition
(H)ARD / Fall - Aortic Regurgitation – Diastolic / Decrescendo
ASS / Bump – Aortic Stenosis – Systolic / Crescendo-Decrescendo
MSD / You – Mitral Stenosis – Diastolic / Decrescendo-Presystolic Crescendo
MRS / Through – Mitral Regurgitation – Systolic / Holo or Pan |
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Term
In Summary What is the differences between Aortic and Pulmonic Stenosis?
ASS BUMP |
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Definition
AORTIC STENOSIS
Pressure Changes:
-decreased Aortic Pulse pressure
-peak LV systolic pressure > Aortic systolic Pressure
-Paradoxical Splitting of S2
MEA (Mean Electrical Axis)
-LVH
-LAD
Murmur louder: Expiration
PULMONIC STENOSIS
-decrease pulse pressure in pulmonary artery
-peak RV systolic pressure > Systolic pressure in pulmonary artery
-Wide splitting of S2
MEA
-RVH
-RAD
Murmur Louder: Expiration
BOTH:
Have a systolic Crescendo-Decrescendo murmur |
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Term
In Summary, What is the differences between Aortic Insufficiency (Regurgitation) and Pulmonic Insufficiency?
(H) ARD FALL |
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Definition
AORTIC INSUFFICIENCY
Pressure Changes:
-Increased Aortic Pulse Pressure (due to increase in LVEDV, increased SV)
MEA:
-LVH
-LAD
Murmur louder: Expiration
PULMONIC INSUFFICIENCY
Pressure Changes:
-Increased Pulmonic Pulse Pressure in pulmonary artery
MEA:
-RVH
-RAD
Murmur louder: Inspiration
BOTH:
-The SV ejected during systole is greater than normal
-There is a Diastolic Decrescendo murmur |
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Term
In Summary, what is the difference between Mitral Valve Insufficiency and Tricuspid Valve Insufficiency?
MRS THROUGH |
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Definition
MITRAL INSUFFICIENCY (Regurgitation)
Pressure Changes:
-Increased pressure and volume in Left Atrium
MEA:
-The elevated atrial pressure can result in hypertrophy of the left atrium (seen as an enlarged P wave).
-Left ventricular hypertrophy can result from a chronic elevation in left ventricular volume.
-LAD
Murmur louder: Expiration
TRICUSPID INSUFFICIENCY
Pressure Changes:
-Increased pressure and volume in Right Atrium
MEA:
-elevated atrial pressure can result in hypertrophy of the right atrium (seen as an enlarged P wave)
-Right ventricular hypertrophy from chronic elevation in right ventricular volume.
-RAD
Murmur louder: Inspiration
BOTH: have a holosystolic/Pansystolic murmur |
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Term
| In Summary, What is the difference between Mitral Stenosis and Tricuspid Stenosis? |
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Definition
MITRAL STENOSIS
Pressure Changes:
-increased pressure in the Left Atrium
-which increases pulmonary venous pressure.
-which increases pressure in pulmonary capillaries and results in pulmonary EDEMA
-Edema will decrease the oxygen level (hypoxia) which causes pulmonary arteriolar constriction
-increase in pulmonary vascular resistance increases pulmonary artery pressure, resulting in right ventricular hypertrophy
-People with this valve dysfunction have a limited ability to increase cardiac output (which may limit physical activity).
MEA:
-A chronic increase in pulmonary artery pressure will result in RVH and RAD
-The elevated atrial pressure can result in hypertrophy of the left atrium (seen as a notched P wave).
Murmur louder: Expiration
TRICUSPID STENOSIS
Pressure Changes:
-increased pressure in right atrium
-which increases pressure in systemic veins
-this increases capillary pressure in systemic organs and results in edema in systemic organs.
-oxygen levels are reduced in systemic organs (hypoxia) which may lead to decrease in TPR slightly.
-Aortic pressure will not be increased so LVH will not occur.
MEA:
-elevated atrial pressure can result in hypertrophy of the Right atrium.
- Aortic pressure will not be increased so LVH will not occur.
Murmur louder: Inspiration
BOTH:
- Impaired filling of the corresponding ventricle (no hypertrophy of these ventricle).
- A diastolic decrescendo-presystolic crescendo murmur |
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Term
| What is common in all structures of vessels? |
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Definition
- All vessels contain a single layer of endothelial cells.
- Smooth muscle surrounds all vessels except capillaries and post-capillary venules. |
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Term
| What are the main functions of Arterioles? |
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Definition
-Increasing arterioloar radius within an organ will decrease vascular resistance in the organ
-decrease vascular resistance will increase blood flow to the organ
-decrease vascular resistance will also increase capillary pressure by having an increase in volume. As a result, there is an increase in filtration of fluid across capillary
Arterioles play a key role in regulation of:
- Organ blood flow
- Filtration by altering capillary pressure |
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Term
| What are the main functions of Precapillary Sphincters |
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Definition
-Precapillary Sphincters are either open or closed
- number of open pre-capillary sphincters determine the number of perfused capillaries
- number perfused capillaries will determine total surface area for exchange
Precapillary sphincters are bands of smooth muscle at the end of arterioles in front of capillaries. |
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Term
| What are the main functions of Capillaries? |
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Definition
CAPILLARIES
Single layer of endothelial cells with no overlying vascular smooth muscle
Site of exchange of nutrients and fluid between blood and tissue
Filtration/reabsorbtion:
-Capillary pressure
-Oncotic pressure of plasma
-Increasing capillary pressure will increase filtration (from capillaries to interstitial to cell)
-Increasing the Oncotic pressure of plasma will increase absorption. |
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Term
| What are the main functions of Post-Capillary venules? |
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Definition
POST-CAPILLARY VENULES
Single layer of endothelial cells with no overlying vascular smooth muscle
Important site of inflammation-induced:
-Leukocyte trafficking (rolls, adhere, enters endothelial tissue)
-Increased vascular permeability |
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Term
| What are the functions of arteriovenous shunts? |
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Definition
ARTERIOVENOUS SHUNTS (METARTERIOLES)
-Blood flows from an arteriole directly to a venule (skipping the capillaries)
-Flow through AV shunts is termed non-nutritional blood flow since no exchange of nutrients occurs with the tissue. |
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Term
| What is the main function of the Lymphatic system? |
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Definition
-Under normal conditions, filtration of fluid slightly exceeds reabsorbtion.
-Lymphatics remove this excess fluid and also small amount of plasma proteins which enters tissue.
The lymphatic system is a one-way system that returns excess interstitial fluid to the cardiovascular system.
This excess fluid enters the lymph capillaries, and flows through the lymphatic vessels and nodes.
All lymphatic vessels converge into larger lymphatic vessels, which empty into the systemic circulation via the systemic veins through the Superior Vena Cava (I think) |
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Term
| What is the equation for Net filtration force? |
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Definition
Net Filtration Force = (Pc - Pi) - (πp - πi)
Pc = capillary pressure πp = oncotic pressure of plasma proteins
Pi = interstitial pressure πi = oncotic pressure of interstitial proteins
Capillary pressure (Pc) declines from the beginning to the end of the capillary.
-In the first half of the capillary, Pc > πp so net filtration occurs.
-In the second half of the capillary, πp > Pc so net absorption occurs. |
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Term
| What are the effects of local changes in arteriolar tone on filtration? |
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Definition
Pressure within a structure of the CV system is proportional to volume of blood within.
If blood volume within a structure increases, pressure increases.
Arteriolar dilation will increase the rate of inflow of blood into the capillaries, increase capillary blood volume, and therefore, increase capillary pressure. (example is when you are exercising. The hypoxia will cause your arterioles to dilate, which will increase pressure and increase the blood flow into the capillaries. This will allow for a greater Oxygen exchange).
Arteriolar constriction will decrease the rate of inflow of blood into the capillaries, decrease capillary blood volume, and therefore, decrease capillary pressure. |
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Term
| What are the effects of venous pressure on filtration? |
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Definition
When venous pressure is increased, the rate of blood flow out of the capillaries decreases, which increases both capillary blood volume and capillary pressure, which will increase capillary filtration, and may lead to edema.
The increase in capillary pressure is greatest near the venous end of the capillary and least at the arteriolar end of the capillary (the beginning of the capillary). (probably due to capillary sphincter) |
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Term
| What happens during congestion? |
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Definition
Congestion occurs when venous outflow is reduced due to local obstruction (i.e., venous thrombosis, edema) or when venous pressure is increased (as in heart failure).
The net result is greater filtration of fluid to the interstitial space because of increase capillary pressure due to the higher venous pressure. |
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Term
What is the effect of decreased oncotic pressure on filtration?
What are the causes of decreased oncotic pressure? |
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Definition
When oncotic pressure is decreased due to reduced plasma protein levels, the force for reabsorption of fluid into capillaries is reduced.
Therefore, net filtration across the capillary is increased.
Conversely,
When oncotic pressure is increased due to increased plasma protein, you will get a greater force for reabsorption into capillaries, and net filtration across the capillary is decreased.
2)
Liver disease: can impair production of plasma proteins in liver. So you have a decrease in plasma protein levels.
Kidney disease: may increase excretion of plasma proteins in urine. You get a decrease in plasma protein level.
Protein malnutrition: impaired plasma protein production. Lower protein in plasma. |
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Term
What is vascular permeability and how does it work?
What is an example? |
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Definition
Endothelial cells contain actin and myosin and these contractile filaments regulate vascular permeability. Contraction of these actin-myosin filaments increases the gap between cells (intercellular clefts), which are the major sites for movement of plasma proteins into the tissue.
An example would be Mast cells?
Mast cells are located around the vessels.
If a person is exposed to an allergen, mast cells can degranulate and release various substances which can increase vascular permeability and dilate arterioles.
When an allergen is recognized:
-mast cells degranulate
-releases histamine, PAF?, etc..
-which will increase Ca++ in endothelial cells
-actin-myosin contraction
-bigger gaps between endothelial cells
-increase in vascular permeability
-increase filtration
-you get an inflammatory response! |
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Term
| How does capillary structure vary between organs? |
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Definition
Continuous: no apparent intercellular opening; “low” type in muscle, nerve and adipose tissue; ”high” type in lymph tissue.
Fenestrated: small gaps that are either closed (endocrine glands and intestinal villi) or open (renal glomeruli).
Discontinuous: large intercellular gaps so high permeability; in liver, bone marrow, and spleen. |
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Term
| What is Vasomotion of precapillary sphincter? |
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Definition
Precapillary sphincters continuously open and close (vasomotion), which determines the number of perfused capillaries, and therefore, total surface area for exchange.
Precapillary sphincters open in response to locally-produced dilators which accumulate in tissue when blood flow is not sufficient to meet metabolic demands of the organ.
An example I could think of is NO which is a vasodilator, which when the blood flow is decreased, there is a greater amount of NO in the blood in that area which will cause the capillary to vasodilate. However, if blood flow is rapid, then NO will be washed away so you don’t get an accumulation. |
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Term
What happens during Lymphatic obstruction?
Give an example where lymphatic obstruction occur frequently?
What is a frequent treatment for the outcome of lymphatic obstruction? |
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Definition
If lymphatics are obstructed, proteins will accumulate in the interstitial space.
This will decrease the oncotic force for reabsorption and promote EDEMA.
During surgery to repair a hernia, the lymphatic vessels in this person’s leg were accidentally severed.
Lymphatic vessels are fragile and very difficult to repair.
As a result, plasma protein that accumulated in the interstitial space of the leg could not be removed through the lymphatics.
The oncotic force for reabsorbtion of fluid was lost and severe edema resulted.
What is the only treatment possible to try to reduce this edema???
-Pressure pants. Increasing pressure in the lower extremities will hopefully push the volume of blood back into the capillary and reduce edema.
Another example is:
Some filaria can infect people in tropical regions. The filaria live in lymphatic vessels and obstruct lymph flow.
As a result, fluid and plasma protein that accumulated in the interstitial space of the legs can not be removed through the lymphatics.
The oncotic force for reabsorbtion of fluid will be lost and severe edema results. |
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Term
| What is the difference between diffusion and bulk flow? |
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Definition
Oxygen diffuses down concentration gradients from alveolar air into pulmonary capillaries and also from systemic capillaries into cells in peripheral organs. Diffusion is effective only over short distances.
Bulk flow due to differences in pressure is used to move substances over long distances. Examples include pulmonary ventilation and flow of blood in the cardiovascular system. |
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Term
| What affect does edema have on metabolic exchange between blood and tissue, and the blood flow? |
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Definition
Edema will cause an increase in interstitial volume, which will cause 2 things:
1. it will increase the diffusion distance between capillaries and cells, which will lead to an impaired exchange of metabolites between blood and tissue.
2. the interstitial pressure is increased, which will compress venules and small veins, which will decrease the radius of the veins and increase venular resistance, thereby decreasing blood flow. |
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Term
| How does Calcium play a role in vasoconstriction? |
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Definition
Contractile activity of vascular smooth muscle is dependent on Ca++ concentration in the cytoplasm, which depends on several processes.
Influx of Ca++ through membrane channels and the release of Ca++ from sarcoplasmic reticulum will positive increase cytosolic Ca++ concentration.
Likewise, CaATPase pumps in SR and plasma membrane will remove intracellular Ca++ , which will decrease contraction.
Increasing Ca++ level will increase cross bridge cycling, which produces contraction! |
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Term
| How is the level of Ca++ in vascular smooth muscle compared to cardiac or skeletal muscle? |
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Definition
Compared to cardiac or skeletal muscle, in vascular smooth muscle:
The rate of cross-bridge cycling is much slower due to a lower ATPase activity. This characteristic allows vascular smooth muscle to maintain sustained tension (vascular tone).
Changes in cytosolic Ca++ are more dependent on influx of extracellular Ca++ rather than release of Ca++ from intracellular stores. This characteristic is the basis for the use of Ca++ channel antagonists to treat some forms of hypertension that was caused by TPR. It treats it by prevent Ca++ from entering the cell, and bringing down hypertension towards normal. |
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Term
| What is a hormone that causes contraction of vascular smooth muscle? And on what receptor does it affect? |
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Definition
Norepinephrine (NE) activates 1 receptors on vascular smooth muscle, which opens receptor-operated Ca++ channels (ROC), which increases Ca++ influx, and also stimulates Ca++ release from the sarcoplasmic reticulum.
Ca++ influx can also occur through voltage-operated Ca++ channels (VOC), which open in response to depolarization.
Note: alpha 1 is part of the baroreceptor reflex |
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Term
| What is the cause of relaxation of vascular smooth muscle? Give a hormone and the receptor it binds to… |
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Definition
Vascular smooth muscle in some organs have β2 adrenergic receptors (mainly in arterioles of skeletal muscle).
These receptors are not innervated but can be activated by circulating epinephrine (EPI), which decreases cytosolic Ca++ levels and relaxes vascular smooth muscle.
Note: beta-2 is part of the Fight or Flight reflex, not baroreflex. |
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Term
| How is Potassium responsible for increasing blood flow to organs? |
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Definition
The mechanism is called Hyperpolarization-mediated vasodilation.
Activation of KATP channels increases organ blood flow when ATP generation is impaired (i.e., hypoxia or ischemia).
When ATP levels decrease, K+ efflux increases causing hyperpolarization of vascular smooth muscle, decreased Ca++ influx, relaxation of vascular smooth muscle and increased blood flow.
Resting membrane potential in vascular smooth muscle is about -50 to -60 mV (which is more positive than nerve, skeletal muscle, and cardiac muscle), so hyperkalemia causes hyperpolarization of membrane potential.
Several vasodilator drugs used clinically to activate KATP channels. |
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Term
| What is an endothelial-derived relaxing factor? |
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Definition
Exogenous acetylcholine (ACh) produced relaxation of arterial segments with endothelial cells, yet in the absence of the endothelium, acetylcholine caused constriction.
These findings have enormous implications to clinical situations involving damage to endothelial cells. We now know that the dilator produced by endothelial cells is nitric oxide (NO).
Ach will cause a release of NO from endothelial cells to relax vascular smooth muscle and it is continually released from endothelial cell. NO is release as a response from Ca. NO is highly diffusible.
Some vasodilators can increase Ca++ entry into endothelial cells, activating nitric oxide synthase, which forms nitric oxide (NO) from L-arginine.
NO is highly permeable and diffuses into underlying vascular smooth muscle, where it decreases intracellular calcium levels and causes relaxation.
NO appears to be continuously produced in nearly all organs. |
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Term
| What is the effect of cytosolic Calcium in endothelial cell as compared to smooth muscle cell? |
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Definition
An increase in intracellular calcium in endothelial cells does not cause vasoconstriction, but causes vasodilation through increased NO production. (remember that increasing cytosolic Ca++ will increase NO production which will promote vasodilation)
-An outcome of increasing Ca++ and NO in endothelial cell is vasodilation which will increase blood flow.
An increase in intracellular calcium in vascular smooth muscle cells causes vasoconstriction.
-An outcome of increasing intracellular Ca++ in smooth muscle cell is vasoconstriction of arterioles which decreases blood flow. |
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Term
How is Nitric Oxide (NO) production inhibited?
When would you want to inhibit NO production? |
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Definition
The NO synthase is responsible for converting L-Arg to Nitric Oxide. A compound called “L-NAME” is responsible for competitively inhibiting NO SYNTHASE.
Increasing L-NAME will decrease NO production, which causes arteriolar constriction, and increase resistance to flow in organ, which will ultimately decrease blood flow to organ.
You would want to inhibit NO production when you get septic shock.
It is bad when you get septic shock b/c the Increase in NO will cause a drastic drop in Blood pressure. You'll have massive Vasodilation throughout your body and much decrease in TPR. |
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Term
What is the normal conditions of LEUKOCYTE-ENDOTHELIAL ADHESIVE INTERACTIONS ?
What happens during inflammation? |
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Definition
The leukocyte will simply flow through the blood stream under normal condition.
During inflammation, the leukocyte will Roll, adhere, then endocytose into the area of infection.
Rolling occurs in post-capillary venules. Rolling allows interaction with other adhesion molecules, such as integrins.
Also, during inflammation, the endothelial cells are contracted, which increases the gap between them and this will increase the vascular permeability.
Proteolytic enzymes and oxidants are released from the leukocytes adherent to venules, which damage the microcirculation. With a local infection, this microvascular injury will not be of any significance.
However, in certain conditions (i.e., sepsis, shock), large numbers of circulating leukocytes become activated and cause damage to the microcirculation in many organs with severe consequences. |
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Term
| How is NO involved in interactions with Adhesion molecule expression? |
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Definition
NO inhibits adhesion molecule expression. NO inhibits adhesion molecules such as P- and E-selectin, ICAMs and VCAMs.
L-NAME (NO synthase inhibitor) will decrease NO production, this allows:
-allowing adhesion molecule expression on endothelial cells
-leukocyte-endothelial adherence
-release of proteolytic enzymes and free radicals
-cause damages to endothelial cells
-increase vascular permeability |
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Term
| How is NO involved with Platelet Aggregation? |
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Definition
Under normal conditions, platelet aggregation is inhibited by nitric oxide and prostacyclin (a prostaglandin), which are produced by endothelial cells.
When endothelial cells are damaged, production of nitric oxide and prostacyclin is decreased and platelets can aggregate and adhere to the vessel wall.
In addition, aggregating platelets release vasoconstrictors, which can reduce blood flow and enhance organ injury.
Platelet aggregation is an important event in thrombus formation in many diseases. |
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Term
| What are the main functions of Nitric Oxide? |
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Definition
•Vasodilator
•Prevents leukocyte and platelet adherence
•Maintains normal low vascular permeability
•Antioxidant (Free oxygen is converted to Superoxide, which will interact with any chemical substances within close proximity; NO prevents this). |
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Term
What is Endothelin-1?
How does ET-1 do it’s job? |
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Definition
ET-1 is a 21 AA peptide. It is formed by endothelial cells.
It is the most potent vasoconstrictor ever found!
Damage to endothelial cell will decrease NO and increase ET-1
ET-1 is a 21 amino acid peptide that is not stored but is synthesized in response to various stimuli. This process is slow (~1 hour). ET-1 formation is also increased following endothelial cell damage (i.e., ischemia/reperfusion, hemorrhagic shock).
ET-1 acts through membrane receptors on vascular smooth muscle cells to cause vasoconstriction by:
a. release of intracellular Ca++
b. influx of Ca++
An extremely unusual characteristic of ET-1 is sustained vasoconstriction.
Damage will decrease vasodilator, increase ET-1, constriction occurs, and increase blood flow to other organs.
ET-1 may lead to hypertension.
ET-1 was injected i.v. at 0 minutes as indicated and produced a sustained increase in arterial blood pressure.
This prolonged vasoconstriction significantly augments organ injury in conditions where ET-1 formation is increased. |
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Term
| What is Ischemia/Reperfusion? |
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Definition
Ischemia is defined as decreased blood flow, while reperfusion is the restoration of blood flow after an ischemic period.
Surprisingly, microvascular injury mainly occurs during reperfusion rather than ischemia. This injury is caused by the reintroduction of oxygen.
Reintroduction of oxygen during reperfusion of organs after prolonged ischemia leads to generation of reactive oxidants, which can inactivate nitric oxide and promotes microvascular injury.
The classic example of ischemia/reperfusion is organ transplantation. |
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Term
| How does Ischemia/Reperfusion work? |
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Definition
After a prolonged ischemia, you reintroduce Oxygen on reperfusion (restoration of blood flow after an ischemic period)
-the oxygen generates Reactive Oxygen Species (ROS), which can do many things:
-1) Damage to endothelial cells, which will increase vascular permeability, which will impair Oxygen delivery.
2) inactivate NO, which will allow leukocyte adherence to venules, which will assist in the increased vascular permeability.
3) Increased formation of ET-1, which leads to arteriolar constriction, which will decrease blood flow. |
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Term
If microvascular injury is developing in an organ after transplantation, could nitric oxide be given since it is an anti-inflammatory agent?
What are potential complications if nitric oxide was given:
-systemically by intravenous infusion?
-or locally by intra-arterial infusion to the transplanted organ? |
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Definition
You cannot administer NO via IV b/c you would dialate everywhere and cause shock.
Because nitric oxide is a potent vasodilator, intra-venous infusion would result in dilation of arterioles throughout systemic organs. This would decrease total peripheral resistance and cause arterial blood pressure to fall (shock).
Local intra-arterial infusion of nitric oxide to the transplanted organ would dilate arterioles within that organ. Local arteriolar dilation would increase blood flow to the organ, and increase capillary pressure, which would promote edema. |
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Term
| At Resting blood flow, what organs make up about 2/3 of cardiac output? |
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Definition
Three organ systems [kidneys (20%), skeletal muscle (21%), liver and gastrointestinal tract (25%)] receive about two-thirds of cardiac output at rest (top panel).
The top panel also shows that the level of blood flow differs between organs.
These differences in flow cannot be attributed to differences in organ weights. When blood flow is expressed per 100 g, there are still marked differences in resting blood flow between organs: from 4 ml/min/100 g in skeletal muscle to 309 ml/min/100 g in the kidneys (bottom panel). |
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Term
| WHY DOES RESTING BLOOD FLOW DIFFER BETWEEN ORGANS |
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Definition
Blood flow to any systemic organ is determined by the following relationship:
Flow of Organ = Pressure Gradient / Resistance in Organ = (MAP – RAP)/Resistance in Organ
The pressure gradient driving blood flow to systemic organs is the difference between mean arterial pressure and right atrial pressure (MAP - RAP).
This pressure gradient is the same for all systemic organs.
Resting blood flow to organs varies because of differences in vascular resistance between organs. |
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Term
| What is the difference between the resting vs maximal organ blood flow? |
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Definition
If all vasoconstrictor nerves are cut and arterioles are maximally vasodilated, blood flow can increase:
-over 20-fold in skeletal muscle
-2 to 3-fold in brain and liver
-5-fold in heart
-only 16% in kidneys.
Resting blood flow varies among organs due to differences in organ vascular resistance.
There are also marked differences in maximal blood flows to various organs.
Therefore, arterioles from various organs have different resting tone and also differ in their ability to dilate.
We have already seen some evidence of these differences:
-beta-2 receptors predominately in skeletal muscle arterioles
-differences in sympathetic nerve innervation density between organs |
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Term
| What influences vascular tone? |
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Definition
Local control of organ blood flow refers to the ability of an organ to adjust organ vascular resistance in response to changes in metabolic needs (primarily related to changes in tissue O2 levels).
Mechanisms responsible for local control of blood flow predominate in heart and brain, and play a lesser role in other systemic organs. |
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Term
What determines Oxygen consumption by systemic organs?
Oxygen uptake depends on what 2 factors? |
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Definition
We saw that there is a wide variation in the ability of an organ to maximally increase blood flow above its resting level.
Maximal blood flow can increase 20-fold in skeletal muscle yet only by 16% in the kidneys.
Since one of the critical roles of blood flow is O2 delivery to an organ, does this mean that the kidneys can only increase their O2 consumption by 16%? – No…
Blood flow is only one factor which determines O2 uptake by an organ.
2)
Oxygen uptake into an organ depends on both (1) the rate of blood flow to the organ as well as the (2) organ's ability to remove (extract) O2 from the blood perfusing it.
O2 Uptake in an Organ = Blood Flow x (A-V)O2 Difference
where (A-V)O2 Difference = O2 Extraction
O2 extraction is the difference in O2 content in arterial and venous blood of an organ. O2 diffuses from blood to tissue across the capillaries of an organ, so the total surface area of perfused capillaries will determine the ability of an organ to extract O2 from blood.
Oxygen uptake can change by - Opening of precapillary sphincters will increase the number of perfused capillaries as well as surface area for exchange, which enhances the ability of an organ to extract O2.
What does the equation above for O2 uptake in an organ resemble? It’s a rearrangement of Fick’s Equation. |
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Term
| What is the difference between the uptake of Oxygen in the heart and Kidneys, as compared to other systemic organs? |
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Definition
In the heart, ALL capillaries are perfused under resting conditions. Therefore, capillary surface area cannot be increased so O2 uptake is dependent on changes in blood flow.
Kidneys can increase capillary surface area by opening pre-capillary sphincters which increases O2 extraction, but renal blood flow cannot increase very much (16%).
Other organs increase O2 uptake by increasing both blood flow and O2 extraction (opening cap sphincter, increase Surface area, which will increase extraction.) |
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Term
What is autoregulation?
When will it be utilize? |
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Definition
AUTOREGULATION represents the ability of an organ to maintain blood flow relatively constant in response to changes in systemic arterial pressure. Changes in arterial pressure initially affect blood flow in all organs (curve A). In organs which autoregulate, blood flow returns toward normal within ~30 seconds (curve B).
Autoregulation can occur only over a certain range of arterial pressure (from ~70 to 180 mm Hg in this example).
When arterial pressure changes, the pressure gradient for flow is altered. How can blood flow remain nearly constant over a wide range of arterial pressure? |
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Term
When arterial pressure changes, the pressure gradient for flow is altered.
How can blood flow remain nearly constant over a wide range of arterial pressure? |
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Definition
AUTOREGULATION: ARTERIOLAR DIAMETER
In the brain and heart (which exhibit autoregulation), flow is maintained nearly con |
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Term
| The mechanism responsible for autoregulation involves what 2 response/metabolites? |
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Definition
1. a myogenic response where changes in intravascular pressure alter stretch of the vessel wall, resulting in constriction or dilation.
-The higher pressure causes an initial increase in diameter due to passive distension of the vessel (stretch). This stretch increases Ca++ entry into vascular smooth muscle cells, causing arteriolar constriction and a decreased diameter compared to its initial value.
This myogenic response increases resistance of the arteriole, which would minimize the increase in flow while pressure is high.
Mechanims: Increase arteriolar pressure – Increase stretch of vessel wall – increase frequency of action potentials in vascular smooth muscle – Ca++ channels open – increase in Ca++ influx – leads to contraction
2. changes in the level of metabolic vasodilators in interstitial fluid of the organ.
-Vasodilator metabolites are produced by cells of many organs.
The interstitial concentration of these vasodilator metabolites will be determined by a balance between two processes:
-Rate of formation (which is proportional to organ metabolic rate)
-Rate of removal (which is proportional to organ blood flow) |
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Term
What are vasodilator metabolites?
What are some examples of vasodilator metabolites? Mechanism?
What are the overall action of vasodilators? |
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Definition
Increased metabolism or decreased blood flow (not pushing the vasodilator away) will cause interstitial concentrations of vasodilator metabolites to rise, resulting in local arteriolar dilation.
A decrease in vascular resistance will increase organ blood flow, which improves O2 delivery to the organ.
Changes in vascular resistance of one organ in most cases do not significantly affect TPR. As a result, there is no change in MAP or CO. The local change in organ blood flow is the result of redistribution of CO among systemic organs.
2) Examples of Vasodilator metabolites
Adenosine levels rise when ATP formation is impaired. Adenosine freely diffuses out of the cell and is a potent vasodilator.
K+ plays a major role in local regulation of blood flow in electrically excitable organs such as the brain and heart. When the frequency of action potentials increases, the interstitial concentration of K+ rises.
-This local hyperkalemia causes hyperpolarization of arterioles within these organs, which decreases Ca++ influx to vascular smooth muscle, and causes relaxation.
Increased interstitial levels of lactic acid, H+ (acidosis), and CO2 occur when O2 demand exceeds O2 availability (due to increased metabolic rate or impaired O2 delivery).
Decreased ATP levels (or increased ADP levels) activates KATP channels, which increases K+ efflux, resulting in local hyperkalemia.
3) All vasodilator metabolites:
-decrease Ca++ levels within vascular smooth muscle,
-resulting in relaxation.
-increased arteriolar radius,
-decreased vascular resistance within the organ,
- and increased organ blood flow. |
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Term
What is Active Hyperemia?
What is an example of Active Hyperemia? |
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Definition
As metabolic rate of the organ increases, blood flow increases due to local arteriolar dilation caused by increased interstitial levels of vasodilator metabolites. The increase in blood flow is proportional to the increase in metabolic activity.
-Increase metabolic activity of organ – will decrease oxygen levels in organ – respond by increasing vasodilator metabolite levels – arteriolar dilation occur – and you get an increase blood flow to organ.
In some organs, when the metabolic rate increases (i.e., during exercise), the arterioles dilate and flow increases (active hyperemia).
-The increase in blood flow is proportional to the increase in metabolic activity.
The mechanism of active hyperemia involves accumulation of vasodilator metabolites in interstitial fluid, which causes arteriolar dilation (and decreased vascular resistance resulting in increased organ blood flow).
Vasodilator metabolites responsible for active hyperemia include:
- adenosine, K+, lactic acid ( pH), CO2 |
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Term
How does Active Hyperemia work during exercise?
2) how does focal active hyperemia work in the brain? |
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Definition
Exercise is an example of active hyperemia in skeletal muscle.
When the metabolic rate of skeletal muscle increases, tissue O2 level decreases resulting in increased formation of vasodilator metabolites.
The decrease in vascular resistance of skeletal muscle will increase skeletal muscle blood flow.
However, because skeletal muscle is such a large fraction of body mass, decreased skeletal muscle vascular resistance will lower TPR.
Mechanism:
-Increase metabolic rate of skeletal muscle:
= decrease in O2 levels in tissue
= response is an increase formation of vasodilator metabolites
= dilation of skeletal muscle arterioles
= decrease vascular resistance in skeletal muscle
= increase blood flow to skeletal muscle
Note: decreases vascular resistance in skeletal muscle will lower TPR.
2)
Many mental functions are localized in well-defined regions, and local neuronal activity increases the local metabolic rate in these areas. The cerebral circulation adjusts flow to meet the varying metabolic rate of each region (active hyperemia).
Neuronal activation produces a local increase in blood flow in discrete areas of the brain. Dark blue corresponds to areas of highest flows, light blue with slight increases in flow, and pink with the level of resting blood flow. |
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Term
| What is the baroreflex response during exercise? (ie of Active Hyperemia) |
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Definition
The decrease in MAP due to lower TPR will initiate a baroreflex response resulting in increased CO.
How will exercise affect systemic arterial pressures?
Low TPR: increased runoff lowers arterial diastolic pressure (this effect is greater than the increase in heart rate which elevates diastolic pressure).
Increased pulse pressure due to increased SV.
Increased arterial systolic and decreased arterial diastolic compared to normal.
Mechanism:
-Decrease vascular resistance in skeletal muscle, will decrease TPR, which will decrease MAP
-decrease MAP will decrease Baroreceptor Reflex/firing:
-This will increase sympathetic firing, which will cause venoconstriction and increase in Inotropic state, which will increase CO
-At the same time, it will decrease parasym firing, which will increase HR and increase CO
Note: in a bee sting, the anaphylactic shock, there is so much histamine that even if SYM firing has increase, it cannot overcome the vasodilation. |
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Term
What is Reactive Hyperemia?
Why does reactive hyperemia occur after a period of occlusion? |
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Definition
Reactive hyperemia refers to a phenomenon where blood flow is transiently increased following a brief period of total ischemia.
A classic example of reactive hyperemia is the increase in forearm blood flow following occlusion of arteries in the upper arm by inflation of a blood pressure cuff above arterial systolic pressure.
When the blood pressure cuff is removed after a brief period, forearm blood flow is immediately higher than its resting level and gradually decreases toward normal levels (this period is known as Reactive Hyperemia).
The degree and duration of this increased flow are proportional to the duration of the occlusion (i.e., to the metabolic debt incurred during reduced flow).
2) Arteriolar dilation occurs during the period of occlusion due to:
1. decreased stretch of arterioles (myogenic response)
2. accumulation of metabolic vasodilators in interstitial fluid of the forearm due to a decreased rate of removal since there is no blood flow.
*Together, these 2 would bring blood flow into the area of ischemia greater than normal |
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Term
| ISCHEMIA/REPERFUSION versus REACTIVE HYPEREMIA |
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Definition
ISCHEMIA/REPERFUSION
Ischemia/reperfusion injury occurs upon restoration of blood flow after prolonged ischemia (30 minutes or more).
During ischemia, enzymatic changes occur in the tissue which cause reactive oxidants to be formed when oxygen delivery increases at the time of reperfusion. Reactive oxidants inactivate nitric oxide, increase endothelin-1 formation, and damage endothelial cells. As a result, Microvascular inflammation occurs along with arteriolar constriction.
REACTIVE HYPEREMIA
Reactive hyperemia is an example of local regulation of blood flow under normal conditions. During a brief period of ischemia due to arterial occlusion, vasodilator metabolites accumulate causing arteriolar dilation in the tissue. When the arterial occlusion ends, blood flow is initially high and decreases as the accumulated vasodilators are washed out of the tissue.
The duration of ischemia is brief (seconds to a 1 or 2 minutes) in reactive hyperemia, while the ischemic period is far longer when microvascular injury occurs in ischemia/reperfusion.
The time difference is what determines I/R vs RH |
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Term
What is so special about the brain?
Where are the sources of blood supply coming from? |
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Definition
The human brain is ~2% of body mass yet receives ~14% of the resting cardiac output with most blood going to the grey matter.
The brain is extremely sensitive to ischemia since it has a very high rate of oxidative metabolism. After just a few seconds of cerebral ischemia, a person loses consciousness and irreversible cell damage occurs within minutes.
Blood reaches the brain through four source arteries:
-Two internal carotid arteries
-Two vertebral arteries
The vertebral arteries form the basilar artery which, along with the carotids forms the Circle of Willis.
The Circle of Willis protects the brain against damage when one of the source arteries becomes obstructed, as the other three source arteries provide flow. |
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Term
| Where is the CSF formed and what is important about it? |
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Definition
The cerebrospinal fluid (CSF) is formed in the ventricles of the brain and differs from plasma mainly by its very low protein content.
An important feature of the cerebral circulation is that it is enclosed within a rigid cavity, the skull. Cerebral blood flow will be impaired due to compression of cerebral vessels whenever intracranial pressure is increased.
Acute elevation of CSF pressure will reduce cerebral blood flow; however, increased CSF pressure will activate the CNS ischemic reflex and arterial pressure will rise. By increasing arterial pressure, cerebral blood flow may improve due to the greater pressure gradient for flow. |
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Term
| What is the blood brain barrier? |
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Definition
Because of their highly selective permeability, the capillaries of the brain are termed the "blood-brain barrier." Most proteins and high molecular weight compounds do not cross the blood-brain barrier.
Lipid-soluble molecules like oxygen and carbon dioxide diffuse freely between plasma and the interstitium.
Brain capillary containing an erythrocyte. The capillary membrane consists of endothelial cells (end) with a tight junction and a continuous basement membrane (bm). |
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Term
What is the autoregulation mechanism of cerebral blood flow?
When MAP is decreased, increased firing of sympathetic nerves occurs via the baroreflex. Why doesn't sympathetic activation cause cerebral arteriolar constriction as it does in other systemic organs?
3) what are the effect of changes in arterial PCO2 and PO2 on cerebral blood flow (CBF). |
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Definition
Cerebral blood flow remains nearly constant over a wide range of arterial pressure (~60 to 160 mm Hg). This is an example of local regulation of blood flow: when MAP increases, cerebral arterioles constrict; when MAP decreases, cerebral arterioles dilate.
In addition to maintaining flow nearly constant, the local arteriolar constriction/dilation helps to minimize changes in cerebral capillary pressure.
2)
The intracerebral arterioles are poorly innervated by sympathetic nerves, so these vessels do not constrict during increased sympathetic activity following reduced MAP.
The brain has a very high metabolic rate, and levels of metabolic vasodilators will increase rapidly in cerebral interstitial fluid when cerebral blood flow initially decreases in response to fall in MAP.
As a result, cerebral arterioles will dilate, lowering cerebral vascular resistance and minimizing the change in cerebral blood flow.
Ultimately: goal is to keep the blood flow constant, not the pressure.
3)
Effect of changes in arterial PCO2 and PO2 on cerebral blood flow (CBF). Increases in PCO2 (i.e., the concentration of CO2 in arterial blood) increase CBF. The steepest part of the PCO2 curve is near 40 mm Hg (which is the normal value for arterial blood), which means that CBF is highly sensitive to small changes in PCO2 at physiological levels. In contrast, CBF changes very little when arterial PO2 changes over the normal range of 80 to 120 mm Hg. |
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Term
Cerebral blood flow did not change until arterial PO2 had decreased from a normal value of ~95 – 100 mm Hg to a PO2 of about 50 mm Hg. This appears to indicate that the brain is not sensitive to hypoxia.
How do we explain these apparently contradictory facts? |
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Definition
We discussed local control of cerebral blood flow, such as autoregulation and active hyperemia. In both of these examples, decreased tissue levels of O2 resulted in increased interstitial fluid levels of metabolic dilators, which caused relaxation of cerebral arterioles and increased cerebral blood flow.
These examples of local control of cerebral blood flow imply that the brain is very sensitive to tissue hypoxia, and that the resulting changes in cerebral blood flow can be viewed as compensations to normalize O2 levels.
However, the figure on the previous slide seems to imply that the brain is not sensitive to hypoxia. Cerebral blood flow did not change until arterial PO2 had decreased from a normal value of ~95 – 100 mm Hg to a PO2 of about 50 mm Hg. This appears to indicate that the brain is not sensitive to hypoxia.
How do we explain these apparently contradictory facts?
When arterial PO2 is lowered from 100 mm Hg to 50 mm Hg, the O2 content in blood decreases a small amount: from 20 ml O2/100 ml blood to ~16 ml O2/100 ml blood. This occurs because of the non-linear shape of the O2 dissociation curve.
Therefore, the brain must still be able to extract sufficient O2 from arterial blood at a PO2 of 50 mm Hg. When PO2 drops further, arterial O2 content drops rapidly and tissue hypoxia would occur in the brain, triggering cerebral arteriolar dilation and increased flow.
Note: Hemoglobin and oxygen dissociation curve is not linear, so even if there is a drop in oxygen partial pressure, it doesn’t necessarily mean that the content has dropped drastically. |
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Term
| What is an important regulator of cerebral flow? |
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Definition
Arterial PCO2 is an important regulator of cerebral flow. Hypercapnia (increased arterial PCO2) causes intense cerebral vasodilation, while hypocapnia (decreased arterial PCO2) causes marked vasoconstriction.
CO2 and H2O form carbonic acid, and so changes in CO2 will alter tissue pH.
The effect of CO2 on cerebral arterioles has been attributed to the importance of maintaining pH in the brain nearly constant (changes in pH can depress neuronal activity).
CO2 is removed from the brain by the blood. If the CO2 level in the brain is low, cerebral arteriolar constriction will reduce blood flow as well as the rate of removal of CO2. The result will be increased CO2 levels within the brain.
Basically: when the pCO2 is high, we would want to increase flow so that Carbonic Acid is not made. Inversely, if the pCO2 is low, we want to constrict the blood flow to maintain the level of CO2 in our cerebral flow. |
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Term
| What are some factors which affect blood flow? |
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Definition
Cerebral blood flow is largely under local control involving changes in production of vasodilator metabolites in response to changes in tissue oxygen levels.
The brain autoregulates its blood flow over a wide range of arterial pressures.
Since the brain is in a rigid capsule, increases in intracranial pressure will decrease cerebral blood flow by compressing the veins, which increases cerebral vascular resistance.
Intracranial pressure can also be increased by blockage of cerebrospinal fluid outflow or by edema resulting from microvascular injury. |
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Term
| What happens in cerebral edema? How is it caused? |
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Definition
What may have caused his confusion?
The fall down the stairs may have caused sufficient trauma to the brain to produce microvascular injury, which may have become more severe over the next few days.
Loss of plasma across damaged vessels within the brain would promote development of cerebral edema by reducing the oncotic pressure gradient, and so reducing the force for reabsorption of fluid from the cerebral interstitial space.
As the edema becomes more severe, intracranial pressure will progressively increase and compress veins, which increases cerebral vascular resistance and decreases cerebral blood flow.
This is the likely underlying cause of his confusion. The swelling is also indicated by the shift of the entire brain laterally. |
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Term
What are the treatments in cerebral Edema?
Will cerebral blood flow remain low indefinitely while the person is hyperventilated? |
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Definition
What treatments are available for cerebral edema?
There are no direct interventions to reduce the severity of microvascular injury presently. However, two approaches have been used (with limited success) that are based on principles that we have learned.
The person can be placed on a respirator and hyperventilated to reduce arterial PCO2 levels, which will cause cerebral arteriolar vasoconstriction. This may not seem logical since this will decrease cerebral blood flow further. However, remember that capillary pressure will be reduced following local constriction of cerebral arterioles, and this will reduce the rate of filtration (and hopefully, the edema).
Will cerebral blood flow remain low indefinitely while the person is hyperventilated?
-No. Eventually vasodilator metabolites will accumulate in the brain and cause cerebral arteriolar dilation. When blood flow decrease, the vasodilator will overcome and restore cerebral blood flow.
Also, Mannitol is another substance that can be used to treat Edema:
Mannitol is a substance which is rapidly excreted by the kidney, causing increased fluid excretion (diuresis).
The rationale for the use of mannitol to treat cerebral edema is as follows: i.v. injection of mannitol would increase solute concentration in plasma (increased plasma oncotic pressure), which would increase the rate of reabsorption of fluid from the interstitial space of the brain.
The goal of this approach is to reabsorb fluid from the interstitial space to the blood before mannitol leaks across damaged cerebral vessels into the tissue (since water can move faster than mannitol), and the mannitol (and reabsorbed fluid) will then be removed from the body by the kidneys. |
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Term
How does the heart receive it’s Oxygen and blood?
What is the relationship between myocardial oxygen consumption and coronary blood flow? |
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Definition
The right and left coronary arteries arise from the aorta:
A. left coronary artery supplies mainly the left ventricle and septum
B. right coronary artery supplies mainly the right ventricle, SA node, and a portion of the left ventricle (somewhat variable in humans).
Most of the venous blood (95%) drains directly into the right atrium.
Relationship between myocardial oxygen consumption and coronary blood flow. As oxygen consumption increases (i.e., higher metabolic rate), coronary blood flow increases almost linearly.
Increased myocardial metabolism results in higher levels of local metabolic vasodilators, which dilate coronary arterioles, decreasing coronary vascular resistance and increasing coronary blood flow (active hyperemia).
The extra O2 required at high work rates is supplied mainly by an increase in coronary blood flow rather than extraction to the tissue. |
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Term
| Is there coronary blood flow during systole? What about Diastole? When is flow highest? |
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Definition
During systole, vessels within the left ventricle are mechanically compressed due to the high pressure developed within the ventricle.
This compression transiently increases coronary vascular resistance, which decreases coronary blood flow during systole.
(Side Note: that this compression would actually increase the venous return of the blood from the heart.)
This effect is greatest in the subendocardium. Because of this, myocardial ischemia and infarctions are more common in the subendocardium than in the epicardium of the left ventricle.
Left coronary blood flow is very low during ventricular systole and highest during ventricular diastole.
Approximately 80% of left coronary blood flow occurs during ventricular diastole.
Because the right ventricle only develops only 1/5 of the pressure produced by the left ventricle during systole, there is little compression of vessels within the right ventricle during systole |
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Term
Does the heart also have autoregulation?
What is the determinant of myocardial oxygen supply? Myocardial oxygen demand? |
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Definition
The heart is able to maintain coronary blood flow nearly constant over a wide range of systemic arterial pressures.
The mechanisms responsible for coronary autoregulation are the same as we discussed earlier (myogenic response and metabolic vasodilators).
Autoregulation is an example of local control of blood flow. Coronary blood flow is maintained nearly constant in spite of changes in the pressure gradient for blood flow (MAP – RAP) by altering coronary vascular resistance.
DETERMINANTS OF MYOCARDIAL O2 SUPPLY:
O2 delivery to the heart will depend on coronary blood flow and O2 content of arterial blood.
Coronary blood flow:
Aortic pressure during diastole is the pressure driving coronary blood flow to the left ventricle.
Coronary vascular resistance
As we have seen, mechanical compression of the vessels within the ventricular wall during systole transiently increases coronary vascular resistance.
Vasodilator metabolites are the main regulators of coronary vascular resistance.
O2 carrying capacity of the blood
A. hemoglobin content
B. oxygenation of blood
DETERMINANTS OF MYOCARDIAL O2 DEMAND
Contractility (inotropic state): the most costly determinant of O2 consumption
-A 100% increase in contractility increases O2 consumption by 200%.
Intraventricular pressure
-A 100% increase in intraventricular pressure will increase O2 consumption by 100%.
Heart rate
-A 100% increase in heart rate will increase O2 consumption by 100%.
End diastolic volume (EDV)
A. volume is proportional to radius3
B. O2 consumption increases by only the cube root of the increase in EDV.
C. A 100% increase in EDV will increase O2 consumption by less than 5%. |
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Term
A person comes into the hospital with severe chest pain.
ATHROMBUS in the RIGHT CORONARY ARTERY has reduced flow by 80%.
After removal of the thrombus by angioplasty, right coronary arterial flow has been restored to normal levels.
However, during the next 6 hours, flow through this vessel progressively decreases by 70% even though systemic arterial pressure is normal. There is no evidence of another thrombus.
What could cause this decrease in coronary flow after angioplasty in this person? |
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Definition
Myocardial Ischemia/Reperfusion
A likely cause of the decrease in coronary blood flow is microvascular injury due to ischemia/reperfusion.
This type of damage could occur after angioplasty restored blood flow in the right coronary artery.
When O2 returned to the tissue after prolonged ischemia, formation of reactive oxidants (ROS) from O2 will occur in endothelial cells.
Reactive oxidants decrease tissue nitric oxide levels, and the loss of this vasodilator would cause arteriolar constriction and reduced blood flow.
Since nitric oxide is anti-inflammatory, its loss will lead to leukocyte adherence to venular endothelium, resulting in increased vascular permeability and edema.
Reactive oxidants can also damage endothelial cells which increases endothelin-1 formation. Endothelin-1 will cause sustained arteriolar constriction. |
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Term
How does the lung receive supply from blood?
How are the capillaries in the lungs different than the systemic capillaries?
How is blood flow distributed in lungs? |
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Definition
The lungs receive two blood supplies:
1. Pulmonary arteries which carry deoxygenated blood to capillaries surrounding alveoli
2. Bronchial arteries supply oxygenated blood to the conducting airways.
2)
Exchange of O2 and CO2 occurs between capillary blood and the alveolar space. Pulmonary capillaries differ from the structure systemic capillaries, which are longer and narrower than capillaries in the lung. Pulmonary capillaries surround the alveoli with multiple anastomoses with other capillaries.
3)
Blood flow is distributed unevenly in the lung of an upright person, with the lowest flow at the top and highest flow at the bottom of the lung. The traditional explanation is that gravity distends vessels at the bottom of the lung (decreasing vascular resistance), while vessels at the top collapse (increasing vascular resistance). However, recent studies have questioned this interpretation. |
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Term
| How is the pulmonary circulation different from the systemic circulation? |
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Definition
The pulmonary circulation differs substantially from the systemic circulation:
Pulmonary blood flow is equal to the entire cardiac output.
Pulmonary vascular resistance is very low compared to total peripheral resistance.
The lung does not exhibit autoregulation.
Sympathetic nerves do not play an important role in regulation of pulmonary blood flow.
Vasodilator metabolites do not play a significant role in regulating vascular resistance.
Tissue hypoxia causes constriction of pulmonary arterioles, while low oxygen levels lead to arteriolar dilation in systemic organs. |
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Term
| What happens during pulmonary hypoxia that is different compared to systemic hypoxia? |
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Definition
Decreases in tissue O2 levels within the lung cause pulmonary arteriolar vasoconstriction. Low O2 levels can occur in a variety of ways, including impaired ventilation, pulmonary edema, or living at high altitude.
If alveoli in an area of the lung have a low O2 level, arterioles in that area will constrict.
**Since a major function of the lung is to oxygenate blood, this hypoxic pulmonary vasoconstriction will shift blood flow from poorly ventilated areas (low O2 levels) to well-ventilated areas of the lung. This characteristic is important in matching ventilation and perfusion in the lung.
If the hypoxia occurs throughout the lungs (as in someone living at high altitude or pulmonary edema), generalized pulmonary arteriolar constriction will occur. This will increase pulmonary vascular resistance and elevate pulmonary artery pressure. A chronic increase in afterload to the right ventricle will result in right ventricular hypertrophy. Chronic pulmonary hypertension can result in right heart failure. |
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Term
How is blood regulated in Gastrointestingal circulation?
What is the function of GI? |
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Definition
An unusual characteristic of the splanchnic bed is the portal circulation, which transports blood from one capillary bed (stomach, spleen, intestine, or pancreas) to another capillary bed (liver).
The liver receives a dual supply for blood flow: oxygenated blood through the hepatic artery (20% of flow) and deoxygenated blood through the portal vein (80% of flow).
Changes in gastrointestinal blood flow are regulated by several hormones as well as local neural reflexes.
Increased parasympathetic activity contributes to increased blood flow in many gastrointestinal organs.
Sympathetic nerves (NE via alpha-1 receptors) cause arteriolar constriction and reduced blood flow.
2)
The gastrointestinal circulation plays an important role in both the secretory and absorptive functions of various organs.
Nutrients are absorbed via intestinal villi which consist of a blind-ended lymphatic vessel (lacteal) and a capillary network. Absorbed fats enters the lacteals while other absorded nutrients enter the capillaries. |
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Term
| In Summary, how is organ blood flow of brain regulated? |
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Definition
BRAIN
Excellent autoregulation of blood flow.
Distribution of blood within the brain is controlled by local metabolic factors.
Vasodilation occurs in response to increased concentration of carbon dioxide in arterial blood.
Little direct effect of the autonomic nervous system on the cerebral vasculature. |
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Term
| In Summary, how is organ blood flow of heart regulated? |
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Definition
HEART
Controlled mainly by local metabolic factors. Excellent autoregulation of flow. Direct sympathetic influences are minor and normally overridden by local factors.
Vessels in left ventricle are compressed during systole so flow to the left ventricle occurs mainly during diastole.
Oxygen extraction is very high at rest, so increased coronary flow provides more oxygen to the tissue when coronary work increases. |
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Term
| In Summary, how is organ blood flow of lung regulated? |
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Definition
Pulmonary blood flow normally is equal to systemic cardiac output.
The lungs have very low vascular resistance compared to the systemic circulation. Pulmonary vascular resistance is approximately 1/5 of total peripheral resistance.
Pulmonary arterial systolic and diastolic pressures are also approximately 1/5 of systemic arterial systolic and diastolic pressures.
Blood flow is influenced by gravity and passive physical forces within the lung (i.e., alveolar pressure).
Pulmonary arterioles vasoconstrict in response to low oxygen levels in lung tissue – this is the reverse of the response of systemic arterioles to hypoxia (which dilate when tissue O2 levels decrease). |
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Term
| In Summary, how is organ blood flow of lungs regulated? |
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Definition
Two capillary beds partially in series with each other; blood from the capillaries of the GI tract, spleen, and pancreas flows via the portal vein to the liver. In addition, the liver also receives a separate arterial blood supply.
Sympathetic nerves cause arteriolar vasoconstriction via alpha-1 adrenergic receptors in response to decreased arterial pressure and during stress.
Active hyperemia occurs following ingestion of a meal and is mediated by local metabolic factors and hormones secreted by the GI tract.
Parasympathetic nerves can cause vasodilation. These nerves do not play a role in the baroreflex response. |
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Term
| In Summary, how is organ blood flow of skeletal muscle regulated? |
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Definition
Controlled by local metabolic factors during exercise.
Sympathetic nerves cause vasoconstriction via alpha-1 adrenergic receptors in response to decreased arterial pressure (through the baroreceptor reflex).
Epinephrine causes vasodilation via beta-2 adrenergic receptors (these receptors are not innervated). This response increases skeletal muscle blood flow during the fight or flight response. Epinephrine-induced activation of beta-2 receptors is not part of the baroreflex response. |
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Term
| What are the classifications of shock? |
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Definition
HYPOVOLEMIC:
-Hemorrhage
-Dehydration
-Burns
-Excessive Fluid Loss
DISTRIBUTIVE
-Septic
-Anaphylactic
-Neurogenic
CARDIOGENIC
-Cardiac Tamponade
-Heart Failure
-Myocardial Infarction
Together, they all lead to a decrease in MAP, which will impair organ blood flow. |
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Term
| What are the characteristic of Hypovolemic shock? |
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Definition
LOW BLOOD VOLUME
Hypovolemic shock
-Decreased blood volume resulting in inadequate cardiac output.
-Also called cold shock because skin feels cold and clammy.
-Low central venous pressure.
HYPOVOLEMIC: ie
-Hemorrhage
-Dehydration
-Burns
-Excessive Fluid Loss |
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Term
| What are the characteristic of Distributive shock? |
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Definition
ARTERIOLAR PROBLEM
Distributive shock
-Generalized systemic vasodilation (decreased TPR).
-Blood volume is initially normal.
-Also called low resistance shock or warm shock since skin feels warm.
DISTRIBUTIVE: ie
-Septic
-Anaphylactic
-Neurogenic |
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Term
| What are the characteristic of Cardiogenic shock? |
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Definition
PUMP PROBLEM
Cardiogenic shock
-Inadequate cardiac output by a diseased or impaired heart.
-Also called congested shock due to pump failure.
-High central venous pressure.
-Skin feels cold and clammy.
CARDIOGENIC: ie
-Cardiac Tamponade
-Heart Failure
-Myocardial Infarction |
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Term
| What is the mechanism of Hypovolemic Shock? |
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Definition
Hypovolemic Shock:
Dehydration/Burns/Hemorrhage/Impaired fluid reabsorption by Kidney/Cholera (leading to diarrhea in GI tract)
-decrease blood volume
-decrease venous return
-decrease EDV
-decrease SV
-decrease CO
-decrease MAP
Hypovolemic shock (i.e., decreased blood volume) can be produced in several ways, including hemorrhage, severe dehydration, burns, or massive fluid loss from damaged kidneys or the gastrointestinal tract.
Decreased blood volume results in reduced venous return, decreased stroke volume (Starling’s law), decreased cardiac output, and decreased arterial pressure. |
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Term
| HOW CAN YOU DISTINGUISH HYPOVOLEMIC SHOCK DUE TO HEMORRHAGE FROM DEHYDRATION? |
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Definition
Hemorrhage and dehydration both cause shock by decreasing blood volume which lowers stroke volume, cardiac output, and MAP.
The difference between the two is their effect on plasma osmolality:
-In hemorrhagic shock, plasma osmolality is nearly normal.
-In dehydration, more water than salt has been lost so plasma osmolality is greater than normal. |
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Term
| During hemorrhagic shock, the person’s pulse would have been described as weak or thready. What is the significance of this finding? |
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Definition
Loss of blood impairs filling of the ventricles.
The initial effect of hemorrhage will be to decrease EDV, resulting in reduced SV.
A reduction in SV will decrease CO and MAP.
Pulse pressure (systolic – diastolic pressure) is directly proportional to stroke volume.
If stroke volume increases (from the same arterial diastolic pressure), arterial pulse pressure will be increased.
**The person’s weak pulse is due to the low stroke volume ejected by the ventricle following the loss of blood.
As a result, the pulse pressure (the difference between systolic and diastolic pressure) will be lower than normal.
It will be more difficult to feel the pulsation of the a peripheral artery and this will reflect the low stroke volume and low cardiac output in this person during hemorrhagic shock.
When blood volume is decreased by up to 20%, arterial pressure is not changed very much even though cardiac output may be decreased by 15-20%.
When blood volume is decreased by more than 20%, both arterial pressure and cardiac output decrease. |
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Term
| How can arterial pressure remain normal when blood volume and cardiac output are both decreased by up to 20%? |
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Definition
MAP = CO x TPR
The baroreflex is designed to maintain mean arterial pressure nearly constant, rather than flow (cardiac output).
Baroreceptor reflex:
-increased SYM and decreased PARA
-major response: arteriolar vasoconstriction resulting in increased TPR
-venoconstriction (to increase venous return)
-increased inotropic state and increased heart rate (but cardiac output is still lower than normal due to low blood volume)
The decrease in MAP following hemorrhage will trigger the baroreflex response resulting in increased SYM firing.
SYM stimulation of the ventricles will increase inotropic state, seen as an upward shift in the Starling curve.
Increased SYM firing will also cause venoconstriction, which promotes filling of the heart. However, the increase in heart rate decreases diastolic filling time, which will decrease EDV.
SV will remain lower than normal. |
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Term
| What is the mechanism of Distributive Shock, specifically Septic Shock? |
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Definition
Trauma/Sepsis/Resuscitation after Hemorrhagic shock/Burns:
These lead to a systemic release of Inflammatory mediators, 2 pathways take place that lead to a decrease in MAP:
1)
-Activation of circulating leukocytes
-leukocyte adherence to venules
-increase vascular permeability
-plasma loss
-decrease venous return
-decrease MAP
2)
-Increase in NO production in endothelial cells
-generalized arteriolar vasodilation
-decrease TPR
-decrease MAP |
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Term
| What is the relationship between rate of runoff and diastolic pressure? |
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Definition
Runoff is the flow of blood from the arterial system to the venous system. This flow is dependent on the systemic arteriolar resistance:
1. Systemic arteriolar dilation (decreased TPR) results in a lower resistance to flow and so a higher rate of runoff, which lowers arterial diastolic pressure.
2. Systemic arteriolar constriction (increased TPR) results in a higher resistance and so a lower rate of runoff, which raises arterial diastolic pressure. |
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Term
| What are the causes of Septic shock? |
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Definition
Septic shock can be caused in several ways:
A. Sepsis: bacteria in blood (bacteremia)
1. Endotoxin, a component of the wall of gram negative bacteria, can trigger systemic release of inflammatory mediators.
B. Without bacteremia
1. Resuscitation following hemorrhagic shock, burns, and trauma can cause tissue injury which may lead to release of inflammatory mediators and subsequent development of septic shock.
Also,
1. The causes of septic shock are still not clearly understood. The diagram below represents one of several potential mechanisms contributing to septic shock.
2. Some inflammatory mediators (i.e., cytokines, lipid inflammatory mediators) cause endothelial cells to express inducible nitric oxide synthase (iNOS).
3. Large amounts of nitric oxide are produced, resulting in generalized arteriolar vasodilation, and decreased TPR. MAP can initially be maintained at nearly normal levels during development of septic shock by a marked increase in cardiac output (hyperdynamic phase).
4. Administration of vasoconstrictors to increase TPR is usually not effective because so much nitric oxide is produced that the vascular smooth muscle does not contract normally (i.e., impaired vascular reactivity).
Mechanism:
-systemic release of inflammatory mediators
-iNOS expression in endothelial cells
-excessive NO production
-generalized arteriolar vasodilation/impaired vascular reactivity
-decrease TPR
-decrease MAP |
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Term
We previously discussed how decreased nitric oxide levels after ischemia/reperfusion cause leukocyte adherence to post-capillary venules.
How can leukocyte adherence occur during septic shock when high levels of nitric oxide are being produced from inducible iNOS? |
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Definition
There are multiple factors that regulate leukocyte adherence to venular endothelium.
Nitric oxide is one factor that is normally anti-inflammatory and prevents leukocyte adherence.
In septic shock, the pro-inflammatory factors outweigh even high levels of nitric oxide and leukocyte adherence to post-capillary venules occurs, resulting in microvascular injury.
In addition to microvascular injury caused by activation of circulating leukocytes, platelets are activated causing microthrombi (disseminated intravascular coagulation). |
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Term
What is the mechanism of distributive shock, specifically Anaphylactic Shock (bee sting)?
What is this shock involved with? |
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Definition
Presence of Allergen:
-mast cell degranulation
-release of Histamine, etc..
-arteriolar vasodilation causing a decrease in TPR
-at the same time, increase vascular permeability, leading to plasma loss to interstitium
-ultimately, decreasing MAP
Anaphylactic shock involves degranulation of mast cells in response to an allergen.
Release of histamine and other mediators will cause generalized arteriolar dilation, decreased TPR, and shock.
Histamine will also increase vascular permeability, which will complicate resuscitation unless corrected (if antihistamines are not given, plasma will leak into tissues when capillary pressure increases as MAP recovers). |
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Term
| What is the mechanism of distributive shock, specifically Neurogenic Shock? |
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Definition
Deep Anesthesia/Pain reflex from deep Trauma/Vasovagal Syncope:
-lead to decreased sympathetic activity
-generalized arteriolar vasodilation
-decreased TPR
-decreased MAP
Neurogenic shock is produced by loss of vascular tone due to inhibition of the normal tonic activity of sympathetic vasoconstrictor nerves.
Common causes of neurogenic shock are deep general anesthesia, pain reflexes associated with severe traumatic injury, and transient vasovagal syncope evoked by strong emotions. |
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Term
| What is the mechanism of Cardiogenic shock, specifically Cardiac Tamponade? |
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Definition
As the pericardial sac surrounding the heart becomes filled with fluid, filling of the heart becomes progressively impaired. This fluid accumulation can result from infection or trauma causing rupture of a blood vessel.
If ventricular filling and EDV are reduced, stroke volume (SV) is also decreased (Starling’s Law).
Therefore, cardiac output (CO) is also reduced, resulting in shock.
Cardiogenic shock results from impaired heart performance (pump failure).
Mechanism:
Trauma/Infection:
-lead to fluid accumulating in pericardial sac
-impaired filling of heart
-decreased SV
-decreased CO
-decreased MAP |
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Term
| What is the compensatory responses to shock? |
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Definition
When you have a decreased MAP, you get a decreased in firing of arterial baroreceptors. This will cause 4 responses:
1) decreased para firing to heart = SA node will increase HR = increase CO = bring MAP towards normal
2)increase SYM firing to the HEART = increase HR and increase Inotropic state = increase SV = increase CO = increase MAP toward normal
3) increase SYM firing to VEINs = constriction of veins = increase venous pressure = increase venous return = increase EDV = increase SV = increase CO = increase MAP toward normal
4) increase SYM firing to ARTERIOLES = arteriolar constriction = increase TPR = increase MAP toward normal
Increased SYM firing will activate:
-beta-1 receptors which increases HR and SV (increased inotropic state)
-alpha-1 receptors which causes arteriolar constriction (increased TPR) and venoconstriction (increased venous return).
-Decreased PARA firing in shock will increase HR. |
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Term
| What is the main function of baroreceptor reflex? |
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Definition
Remember that MAP = CO x TPR and CO = HR x SV.
All of these compensatory responses will not play significant roles in the response to each type of shock, as we will see.
If you identify the cause of shock (decreased CO or decreased TPR), the major baroreflex compensation will be an increase in the other factor (in either CO or TPR).
MAP = CO x TPR
The major compensatory response will depend on the initial problem leading to each form of shock.
If decreased CO is the cause of shock, the major baroreflex compensation will be increased TPR.
If decreased TPR is the cause of shock, the major baroreflex compensation will be increased CO. |
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Term
| What are the baroreflex compensations in these 3 shocks? |
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Definition
Hypovolemic shock-----
Initial Problem: decreased blood volume, decreased CO, low CVP (Central Venous Pressure)
Compensatory Response: increase TPR
Secondary Complication: increased vascular permeability
Distributive Shock----
Initial Problem: decreased TPR
Compensatory Response: increase CO
Secondary Complication: Increased vascular permeability
Cardiogenic Shock ----
Initial Problem: decreased CO, high CVP
Compensatory Response: increase TPR
Secondary Complication: pulmonary edema |
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Term
| What is the difference between hypovolemic and cardiogenic shock? |
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Definition
Hypovolemic and cardiogenic shock both have low cardiac output; however, the causes differ:
Hemorrhagic shock: decreased blood volume, decreased central venous pressure.
Cardiogenic shock: impaired pump function, increased central venous pressure. When you press on the abdomen and see a pulsation in the person’s jugular vein (hepatojugular reflux), this is an indication of high central venous pressure. |
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Term
If cardiac output is higher than normal in a person with septic shock, systemic organs are receiving more blood flow than normal.
Even though arterial blood pressure is low, why in septic shock a significant problem is cardiac output being high?
Do we want high flow to all organs? |
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Definition
Total blood flow to systemic organs (cardiac output) is higher than normal in a person with septic shock.
The generalized dilation of systemic organs will result in higher than normal blood flow to some organs but it will also cause lower than normal blood flow to other organs (such as heart and brain which have the highest metabolic activity).
The ability to regulate blood flow to organs based on differences in organ vascular resistance is lost in a person with septic shock.
In addition, increased vascular permeability results in tissue edema which impairs oxygen uptake in systemic organs.
The oxygen demand of the heart is increased much more than normal in order to maintain the high cardiac output, and the heart will eventually fail.
Do we want high flow to all organs? NO!
By dialating the arterials, we perfuse organs that don't need a lot of blood. So we lose ability to regulate perfusion to organs that don’t need it. We could harm the Heart, Brain and Kidneys. |
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Term
| What is the compensatory changes in microcirculation during shock? |
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Definition
During hypotension, blood volume will increase to some extent due to reabsorption of interstitial fluid across the capillaries and venules.
Since MAP is low, intravascular pressures will be low throughout all segments of the vasculature (i.e., artery, arteriole, capillary, venule, vein).
The lower capillary pressure will markedly reduce the rate of filtration.
Net reabsorption of interstitial fluid across capillaries and post-capillary venules will occur due to the oncotic pressure of plasma protein.
Net reabsorption of interstitial fluid will allow an increase in plasma volume, blood volume and this will increase the venous return. Ultimately, bringing MAP up to normal. |
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Term
| What are the treatments for shock? |
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Definition
Hypovolemic Shock ----
Initial Problem: decreased blood volume, decreased CO, low CVP (central venous pressure)
Treatment: Volume resuscitation
Distributive shock----
1) Anaphylactic neurogenic shock
Initial Problem: decreased TPR
Treatment: Vasoconstrictors, antihistamines with anaphylactics
2) Septic shock
Initial Problem: decreased TPR
Treatment: antibiotics?
Cardiogenic Shock----
Initial Problem: decreased CO, high CVP
Treatment: remove blood from the pericardial sac. |
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Term
| What are some quick assessments that you could make for Shock? |
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Definition
For a quick initial assessment:
1. First assess central venous pressure (CVP).
A. If CVP is high: cardiogenic shock.
B. If CVP is low: hemorrhagic or distributive shock.
2. Feel the skin to try to distinguish hemorrhagic from distributive shock.
A. If skin is cold and clammy, this is suggestive of high TPR (decreased skin blood flow following arteriolar vasoconstriction due to increased SYM activity): consistent with hemorrhagic shock or cardiogenic shock.
B. If skin is warm, this indicates low TPR (marked peripheral arteriolar vasodilation leading to increased skin blood flow: this is called the hyperdynamic phase of septic shock).
3. Look at the initial problem in each form of shock to decide on the best approach for treatment. |
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Term
| Vasoconstrictors are not usually effective in treatment of hemorrhagic or cardiogenic shock. Why not? |
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Definition
| TPR is already very high due to SYM activation via the baroreceptors, resulting in generalized arteriolar vasoconstriction. |
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Term
| If excessive NO is a problem in septic shock, why can’t these patients be given an inhibitor of NO synthesis (i.e., L-NAME) to treat the hypotension? |
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Definition
L-NAME will inhibit both constitutive and inducible nitric oxide synthase.
Although L-NAME would increase TPR, inhibition of all NO production would lead to massive leukocyte adhesion to venules and further microvascular injury.
A major effort is currently being made to develop selective inhibitors of inducible nitric oxide synthase that do not affect constitutive nitric oxide synthase. |
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Term
| When would a person experience irreversible shock? |
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Definition
After a certain time of prolonged shock (i.e., progressive stage), irreversible shock develops.
In this stage, death will ensue regardless of treatment. Even if a transfusion is given and cardiac output and arterial pressure improve, death will soon occur.
The progressive stage would occur between 35 to 90 minutes. However, irreversible shock usually occurs between 60-90 minutes. Any transfusion during the irreversible shock period would result in death, regardless. |
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Term
| What are the causes of irreversible shock? Mechanism? |
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Definition
When organ blood flow is reduced for a prolonged period, a series of events occur which will lead to further problems even if a transfusion is given to improve blood pressure.
For example, (1) impaired oxygen delivery leads to accumulation of vasodilator metabolites (i.e., adenosine, K+). These metabolites will dilate arterioles and tend to keep TPR low.
(2) When oxygen delivery is impaired sufficiently, anaerobic metabolism will occur resulting in accumulation of lactic acid. The acidosis due to lactic acid will impair cell function. Excitable tissues such as nerves and muscles (cardiac, skeletal, vascular) are particularly sensitive.
Acidosis = Impaired oxygen delivery to tissues leads to anaerobic metabolism, generation of lactic acid, and decreased arterial pH (acidosis).
(3) Cell injury or death can result in release of toxic factors into blood, including myocardial depressant factor. This factor impairs function of the heart, leading to impaired contractile ability (decreased CO), further contributing to shock.
Ultimately these 3 events will lead to irreversible shock. |
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Term
| After prolonged shock, transfusions which increase arterial pressure can sometimes increase the severity of microvascular injury. How could this occur? |
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Definition
Increased arterial pressure after transfusions would restore blood flow to organs that may have been ischemic for a prolonged time. This situation is basically a problem of systemic ischemia/reperfusion.
Microvascular injury will be increased due to the events we discussed for local ischemia/reperfusion:
1. formation of reactive oxidants (free radicals) from oxygen
2. inactivation of nitric oxide
3. leukocyte adherence to post-capillary venules
4. endothelial cell injury
5. increased endothelin-1 formation
These events would cause arteriolar vasoconstriction and increase vascular permeability. |
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Term
At what arterial pressure would we consider a person to be hypertensive?
What are the 3 ways a person could have hypertension?
What are the causes of Hypertension? |
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Definition
Systemic arterial hypertension is defined as:
1. diastolic arterial pressure > 90 mm Hg.
2. systolic arterial pressure > 140 mm Hg.
Since MAP = CO x TPR, hypertension is due to:
1. increased cardiac output (CO)
2. increased TPR (total peripheral resistance)
3. increased CO and increased TPR
The cause of hypertension (etiology) is the underlying mechanism(s) responsible for the increase in CO, TPR, or both that results in high blood pressure.
Only knowing that CO, TPR, or both are elevated does not define the cause of hypertension. |
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Term
| What are the two classification of hypertension? |
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Definition
PRIMARY HYPERTENSION:
-Hypertension in which the underlying cause is unknown is called essential (or primary) hypertension.
-More than 95% of cases of hypertension are of this type.
SECONDARY HYPERTENSION:
-If the underlying cause of the increased CO or TPR is known, this is termed secondary hypertension.
The cause of hypertension can only be identified in 5% of cases. |
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Term
What is primary (essential) Hypertension?
How is hypertension induced when we get older? |
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Definition
95% of hypertensive individuals.
No definable underlying cause of essential hypertension.
Likely results from interaction of multiple defects in blood pressure regulation with environmental stressors.
May be genetic predisposition.
The cause of increased CO or increased TPR in a person with primary hypertension is not known.
Ongoing research suggests several possibilities may be involved:
-Microvascular dysfunction: decreased levels of nitric oxide (NO) and increased levels of endothelin-1
-Abnormal function of the Na/K ATPase resulting in elevated cytosolic Ca++ levels (some people with primary hypertension have elevated levels of ouabain, a cardiac glycoside which inhibits the Na/K ATPase)
Note: as you grow older, your hypertension is first initiated by a decreased in CO which will lead to an increase in TPR. This TPR will begin to rise over time.
In people with essential hypertension under 40 yrs of age, high blood pressure is mainly due to high CO with normal TPR.
As people age, elevated TPR becomes increasingly responsible for essential hypertension as the heart and blood vessels adapt to chronically high pressure:
a. arterioles hypertrophy in response to high blood pressure, which reduces lumen diameter and increases contractile force: this results in progressive increases in TPR over time.
b. decreased ventricular compliance due to ventricular hypertrophy impairs diastolic filling of the heart. |
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Term
| What is secondary hypertension and what percentage of this is actually identified? |
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Definition
5% of hypertensive individuals
Definable underlying cause of either increased CO, increased TPR, or both in secondary hypertension
*Renal parenchymal disease
Renovascular disease
Pheochromocytoma
Hypothyroidism
Hyperthyroidism
Endothelial Cell Dysfunction |
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Term
| What is Renal Parenchymal Disease? |
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Definition
Renal disease can impair the ability of the kidney to excrete sodium and water.
Mechanism:
Nephron is damaged, this impaired the renal excretion of Na+ and H20. This results in:
- increased blood volume, increase venous pressure, increased preload, increased stroke volume, increased cardiac output, and elevated mean arterial pressure. |
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Term
| What is Renovascular Hypertension? |
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Definition
Renovascular hypertension can result from atherosclerotic plaques in the renal artery.
Reduced renal blood flow increases renin secretion, which elevates circulating angiotensin II levels (ANG II). Angiotension II formation affects 3 pathways:
(1) Increased ANG II levels will stimulate increased release of aldosterone from the adrenal gland, which promotes increased reabsorption of sodium and water by the kidney (resulting in increased blood volume).
(2) Renovascular hypertension is due to increased TPR (arteriolar constriction) as well as (3) increased CO (increased blood volume due to increased aldosterone levels, and increased stroke volume due to elevated venous return as a result of ANG II-induced venoconstriction). |
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Term
| What is Pheochromocytoma? |
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Definition
Pheochromocytomas are catecholamine-secreting tumors, usually in the adrenal medulla.
The release of norepinephrine (NE) and epinephrine (EPI) from the tumor cells can promote vasoconstriction, increased inotropic state, and tachycardia.
Although EPI has a higher affinity for beta-2 receptors than alpha-1 receptors, the circulating levels of EPI are so high that it activates alpha-1 receptors on arterioles (increased TPR) and veins (increased venous return).
The resulting hypertension is due to both increased TPR and increased cardiac output. |
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Term
Can thyroid abnormalities lead to hypertension?
Hypothyroid vs Hyperthyroid? |
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Definition
Both hypothyoidism and hyperthyroidism can cause hypertension.
Approximately 1/3 of hyperthyroid patients and 1/4 of hypothyroid patients are hypertensive.
The underlying cause of hypertension is different in these situations.
Hypothyroid-induced hypertension involves decreased production of metabolic vasodilators as a result of a lower metabolic rate.
*The resulting hypertension is due to increased TPR, increased MAP.
Hypertension due to hyperthyroidism involves abnormally elevated cardiac output due to increased metabolic rate.
-The high levels of thyroxine in these patients increases O2 consumption by systemic organs.
*Total blood volume will be increased in these patients, which is the major cause of increased cardiac output. |
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Term
| How is the baroreceptor changed in patients with hypertension? |
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Definition
After chronic increases in arterial pressure, baroreceptor sensitivity to changes in arterial pressure is decreased compared to a normotensive person.
Compare the points indicated by the squares: the baroreceptor firing rate is the same in the normotensive and the hypertensive person, yet mean arterial pressure is markedly higher in the hypertensive person.
The cause is not known. |
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Term
| In summary, what are the dysfunctions that aid in development of Hypertension? |
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Definition
HEART:
-High CO due to abnormal neuronal or hormonal stimulation may contribute to hypertension.
-Some hypertensive people show abnormal heart rate acceleration under stress.
BLOOD VESSELS:
Hypertension due to increased TPR or increased CO due to greater venous return could result from:
a. Greater than normal sympathetic vasoconstrictor responses
b. Abnormal regulation of vascular tone by local metabolic vasodilators
c. Ion channel defects in vascular smooth muscle
d. Endothelial dysfunction
e. Increased circulating levels of vasoconstrictors
KIDNEY:
Can cause hypertension by increasing blood volume as a result of:
a. impaired renal blood flow (i.e., plaque in a renal artery)
b. inappropriate hormonal regulation (i.e., causing increased aldosterone release
c. ion channel defects causing sodium retention
-Can also increase TPR and venous return through increased renin release resulting in higher circulating angiotensin II levels.
BARORECEPTOR DESENSITIZATION:
In a hypertensive person, this will maintain MAP at a pressure higher than normal.
ADRENAL GLAND:
-Increased release of aldosterone will raise blood volume and increase CO.
-In pheochromocytoma, excessive release of norepinephrine and epinephrine will increase TPR and CO.
CENTRAL EFFECTS:
-Dysfunction in the cardiovascular center can:
-Increase basal sympathetic tone (increasing CO and TPR)
-Result in improper processing of baroreceptor input (and lead to higher sympathetic nerve firing and decreased parasympathetic nerve firing than normal) |
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Term
Hypertension has what effect on the Left ventricle?
What would the Pressure Volume curve look like in someone with chronic increase in afterload/hypertension? |
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Definition
The chronic increase in afterload will cause left ventricular hypertrophy (seen as left axis deviation).
The hypertrophied ventricle can generate more force at any volume compared to the normal ventricle. This is seen as a leftward shift in the Po curve.
Because the hypertrophied ventricle has a lower compliance than normal, the diastolic filling curve will shift up compared to normal.
At the same end diastolic volume, end diastolic pressure will be higher in the hypertrophied ventricle compared to normal. |
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Term
| What organs are damaged from hypertension? |
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Definition
Workload of the heart is increased and oxygen delivery is compromised
-Ventricular hypertrophy and the higher arterial pressure significantly increases myocardial O2 consumption.
-Larger myocytes enhances the chance of impaired O2 delivery (myocardial ischemia resulting in ST segment elevation or depression).
Arterial damage:
-This occurs due to the combined effects of the elevated arterial pressure and accelerated atherosclerosis.
-The high arterial pressure that arteries are subjected to in a hypertensive person may cause endothelial dysfunction.
-Endothelial damage will promote thrombus formation and increase the likelihood of a stroke.
-Physical rupture of an artery (aneurysm) can also occur due to the high arterial pressures. |
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Term
| Can heart failure occur due to hypertension? |
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Definition
In heart failure:
Systolic dysfunction can develop as seen by a rightward shift in Po curve. As a result, the ventricle is able to develop less force and pressures are reduced.
Diastolic function can also develop in heart failure and is seen as an upward shift in the diastolic filling curve. As a result, it is harder to fill the ventricle and ventricular end-diastolic pressure is increased.
Either systolic or diastolic dysfunction or both can develop in heart failure.
Stroke work (the area of the pressure-volume loop) is markedly reduced when systolic and diastolic dysfunction develops. |
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Term
| Is there a treatment for hypertension? What is it? |
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Definition
(1) Lifestyle changes to reduce risk factors:
-Decrease body weight
-Reduced salt intake
-Exercise
-Reduced alcohol consumption and smoking
(2) Pharmacologic therapy:
-Beta blockers, Ca++ channel blockers would help decrease heart rate and decrease inotropic state, decreases CO and SV, leading to a decrease in MAP
-Diuretics, RAS blockers, Alpha blockers, Ca++ channel blockers to decrease the blood volume and decrease venous tone, ultimately decrease CO and decrease MAP back to normal.
-RAS blockers, alpha blockers, central alpha-2 agonist would help with circulating factors and decrease sympathetic innervation, which would lead to a decrease in TPR, bringing MAP down towards normal.
(3) Sympatholytic Agents (Adrenoceptor Antagonists)
alpha-1 antagonists:
-Decrease TPR through relaxation of arteriolar vascular smooth muscle
-Decrease CO by reducing venous return through relaxation of veins
β blockers:
-Reduce cardiac output by: Decreasing both heart rate and inotropic state
(4) Renin-Angiotensin System Antagonists
Angiotensinogen converting enzyme (ACE) inhibitors:
1. Reduces formation of ANG II which will result in:
-Systemic arteriolar dilation (decreased TPR)
-Venodilation leading to reduced venous return (decreased CO)
2. Decreased ANG II levels will reduce aldosterone levels which will result in:
-Decreased blood volume leading to reduced venous return (decreased CO)
Angiotensin II receptor antagonists:
-Effects are similar to ACE inhibitors
(5) Calcium Channel Blockers
Act by decreasing cytosolic calcium levels which will result in:
- Decreased TPR through relaxation of arteriolar vascular smooth muscle
- Decreased CO due to reduced:
Venous return (through relaxation of veins)
Stroke volume (by lowering inotropic state)
Heart rate
(6) Diuretics
Reduce blood volume by increasing renal excretion of water
-This results in decreases in venous return and stroke volume.
-Used to treat hypertension in which CO is elevated (when central venous pressure is abnormally high) |
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Term
| What is the definition of heart failure? |
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Definition
Heart failure is defined as the inability of the heart to pump blood at a rate adequate to meet the metabolic demands of the body.
The degree of heart failure is commonly related to the degree of physical activity. |
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Term
| What is the NEW YORK HEART ASSOCIATION FUNCTIONAL CLASSIFICATION OF HEART FAILURE ?? |
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Definition
Class I - No limitation. Ordinary physical activity does not cause symptoms.
Class II - Slight limitation of physical activity. Ordinary physical activity will result in symptoms.
Class III - Marked limitation of physical activity. Less than normal activity leads to symptoms.
Class IV - Inability to carry on any activity without symptoms. Symptoms are present at rest. |
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Term
| What are the pathophysiology of Heart failure? |
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Definition
Heart failure can result from a wide variety of cardiovascular insults. The etiologies can be grouped into those that cause heart failure because of:
1. impaired contractility
2. increased afterload
3. impaired ventricular filling |
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Term
| What causes Left-Sided Heart Failure? |
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Definition
1) Impaired Contractility due to:
-Myocardial Infarction
-Chronic volume overload
-Transient myocardial ischemia
-Dilated cardiomyopathy
2) Increased Afterload due to:
-Aortic stenosis
-Hypertension
(1) and (2) are systolic dysfunctions, resulting in Left-sided Heart failure
3) Impaired ventricular relaxation due to:
-Left ventricular hypertrophy
-Hypertrophic cardiomyopathy
-Restrictive cardiomyopathy
-Transient myocardial ischemia
4) Obstruction of ventricular filling due to:
-Mitral stenosis
- Pericardial tamponade
(3) and (4) are diastolic dysfunctions, resulting in Left-sided Heart Failure. |
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Term
| What causes Right-Sided Heart Failure? |
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Definition
1) Impaired Contractility due to:
-Myocardial infarction
-Chronic volume overload
-Transient myocardial ischemia
-Dilated cardiomyopathy
2) Increased Afterload due to:
-Pulmonic stenosis
-Pulmonary hypertension
(1) and (2) are Systolic Dysfunctions, which would lead to Right-Sided Heart Failure.
3) Impaired Ventricular Relaxation due to:
-Right ventricular hypertrophy
-Hypertrophic cardiomyopathy
-Restrictive cardiomyopathy
-Transient myocardial ischemia
4) Obstruction of Ventricular Filling due to:
-Tricuspid stenosis
-Pericardial tamponade
(3) and (4) are diastolic dysfunctions, which can lead to Right-Sided Heart Failure |
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Term
| What can result in Axis Deviation? |
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Definition
Normal MEA:
0 to 90o
LAD
More negative than 0o
Ie. Pregnancy
LVH:
Hypertension
Aortic stenosis
Aortic insufficiency
RAD
More positive than 90o
Ie. Infarct in LV
RVH:
Pulmonic stenosis
Pulmonic insufficiency
Mitral stenosis
Living at altitude for months |
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Term
Hypertrophy of ventricular myocyte increases diffusion distance to interior of cell.
This can lead to what type of cardiac dysfunction? |
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Definition
The greater size of myocytes in a hypertrophied heart increases the diffusion distance for movement of O2 from capillaries to the interior of the myocyte. This increases the likelihood of decreased O2 levels within myocytes. A hypertrophied ventricle also consumes more O2 than normal so myocardial ischemia may occur (especially upon increased effort).
Increased Heart Size and mass / Fibrosis / Inadequate Vasculature can lead to:
Cardiac Dysfunction:
-Heart Failure (Systolic/Diastolic Dysfunction)
-Arrythmias
-Neurohumoral Stimulation |
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Term
Is ventricular hypertrophy ever beneficial?
How is the progression of heart failure initiated?
What is Systolic Dysfunction? |
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Definition
Conditions which result in pressure and/or volume overload increase cardiac work, which eventually leads to ventricular hypertrophy.
Hypertrophy initially has beneficial effects by increasing cardiac output.
However, the hypertrophied ventricle has a greater total O2 demand than normal and O2 supply will eventually become insufficient to meet the needs of the heart.
Eventually the heart will begin to fail, although the mechanisms responsible are still not completely known.
2)
As heart failure develops, cardiac output decreases which results in lower MAP.
The baroreflex compensatory responses to low MAP (which are normally beneficial) will accelerate development of heart failure. We’ll look at these mechanisms later in these lecture.
A person diagnosed with heart failure has a greater than 50% mortality at 5 years. |
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Term
| What is Systolic Dysfunction? |
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Definition
Systolic dysfunction is defined as a diminished capacity to eject blood from the affected ventricle due to either impaired myocardial contractility or increased afterload.
Decreased contractility can result from:
1. destruction of myocytes (i.e., myocardial infarction)
2. impaired myocyte function
3. fibrosis |
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Term
What is the equation for CO and PBF?
What is the equation for SV?
What is the equation for Ejection Fraction? (EF)
What are the EF for systolic and diastolic dysfunction? |
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Definition
CO = HR x SV & PBF = HR x SV
CO= cardiac output (liters/min)
PBF= pulmonary blood flow (liters/min)
HR= heart rate (beats/min)
SV= stroke volume (volume of blood ejected per beat
Since the left and right hearts are arranged in series, they must (on average) pump the same amount of blood per minute (i.e., cardiac output equals pulmonary blood flow).
Since the HR is the same for each side, SV must be the same for each ventricle (on average).
In heart failure of either ventricle, both cardiac output and pulmonary blood flow will be reduced compared to normal.
END-DIASTOLIC VOLUME (EDV): the maximal ventricular volume at the end of filling
END-SYSTOLIC VOLUME (ESV): the minimal ventricular volume at the end of ejection
STROKE VOLUME (SV): volume ejected in a single beat
SV = EDV - ESV
EJECTION FRACTION (EF)= SV / EDV
normal range is 0.5 to 0.7 and is an index of contractility of the heart.
-With systolic dysfunction, the ejection fraction will be lower than 0.5.
-With diastolic dysfunction, the ejection fraction will be in the normal range |
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Term
What would the pressure volume loop look like in systolic dysfunction?
How can you tell if a person has Left systolic vs diastolic dysfunction? |
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Definition
The downward shift in the Po curve results in:
1. decreased mean arterial pressure.
2. decreased arterial systolic pressure.
3. the aortic valve closing at a higher end systolic volume than normal.
4. increased end diastolic volume, which helps to minimize the decrease in stroke volume despite lower contractility**
5. increased end diastolic pressure.
6. decreased ejection fraction compared to normal.
Left Ventricular Systolic Dysfunction:
The Po curve is shifted downwards in the patient compared to the healthy person. This indicates that the person has systolic dysfunction.
Same passive filling curve for patient and healthy person so patient does not have diastolic dysfunction
Increased EDV in patient compared to healthy person |
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Term
| What is Diastolic Dysfunction? |
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Definition
Diastolic dysfunction is defined as impaired ventricular filling due to:
1. increased stiffness of the ventricular wall (i.e., ventricular hypertrophy, fibrosis, restrictive cardiomyopathy).
2. reduced ventricular relaxation during diastole. This can be caused by impaired energy production/cellular metabolism in myocytes such that cytosolic calcium remains elevated during diastole. As a result, some cross-bridges remain present during diastole, which impairs passive stretch of the ventricle and impairs filling. |
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Term
| What does diastolic dysfunction look like in a pressure volume curve? |
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Definition
The upward shift in the diastolic filling curve results in:
1.impaired filling of the ventricle
2.decreased end diastolic volume.
3.decreased stroke volume.
4.decreased arterial systolic pressure.
5.decreased mean arterial pressure.
6. increased end diastolic pressure.
However, ejection fraction is not decreased below normal (0.5 to 0.7).
The graph will have the same Po line; however, in Diastolic heart failure, there will be a decreased in EDV (and since it is the same Po line, there will be a change in SV even though the pressure at ESV is the same.) |
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Term
| What happens if you have both systolic and diastolic dysfunction, what would that look like in a P vs V loop? |
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Definition
Systolic and diastolic dysfunction will result in:
1.impaired filling of the ventricle.
2.decreased stroke volume.
3.decreased arterial systolic pressure.
4.decreased mean arterial pressure.
5.decreased stroke work.
6.increased end diastolic pressure.
7.decreased ejection fraction. |
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Term
What does Arterial Pulse pressure look like in someone who heart failure?
Is arterial pulse pressure proportional to stroke volume? |
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Definition
The pulse in a systemic artery (i.e., brachial artery) will feel weaker than normal in a person with heart failure.
Pulse pressure is the difference in arterial systolic pressure and arterial diastolic pressure.
This reflects a decrease in stroke volume in this person.
In the same person, changes in arterial pulse pressure (systolic – diastolic pressure) are directly proportional to changes in stroke volume (SV).
In heart failure, the reduced stroke volume will decrease arterial pulse pressure. |
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Term
| What are the common Symptoms and physical findings in heart failure? |
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Definition
Symptoms / Physical Findings
Left-sided
-Dyspnea / Diaphoresis (sweating)
- Orthopnea / Tachycardia
- Paroxysmal nocturnal dyspnea / Pulmonary rales
- Fatigue / Pulmonary edema
Right-sided
- Right upper quadrant discomfort (due to hepatic enlargement ) / Jugular venous distention & Peripheral edema
- Fatigue / Diaphoresis (sweating) & Tachycardia |
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Term
| WHAT IS THE CAUSE OF EDEMA IN HEART FAILURE? |
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Definition
We saw earlier that ventricular end-diastolic pressure was increased compared to normal in both systolic and diastolic dysfunction.
When pressure is increased in a structure in the cardiovascular system, pressures upstream to this structure will also be increased.
An increase in interstitial fluid volume (edema) occurs in an organ when:
Capillary pressure increases due to:
-Local arteriolar dilation
- Increased venous pressure (important in heart failure)
Oncotic pressure decreases (decreased plasma protein)
Vascular permeability increases due to:
-Mast cell degranulation
- Leukocyte adherence to post-capillary venules
Lymphatic vessels are obstructed |
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Term
| What are the EFFECTs OF INCREASED VENOUS PRESSURE ON FILTRATION |
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Definition
When venous pressure is increased, the rate of blood flow out of the capillaries decreases, which increases both capillary blood volume and capillary pressure.
The increase in capillary pressure is greatest near the venous end of the capillary and least at the arteriolar end of the capillary (the beginning of the capillary). |
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Term
Right-sided heart failure will increase systemic venous pressure and systemic capillary pressure, leading to edema in systemic organs.
Left-sided heart failure will increase pulmonary venous pressure and pulmonary capillary pressure, leading to pulmonary edema.
Why is edema a significant problem? |
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Definition
An increase in interstitial fluid volume (edema) will increase the diffusion distance between capillaries and cells, which will impair O2 delivery to cells.
In addition, the increased interstitial pressure due to edema will compress venules and veins, causing further increases in capillary pressure and reduced organ blood flow.
Pulmonary Edema:
-Pulmonary edema will impair diffusion of oxygen from alveolar air into the lung. This will lower O2 levels within the lung, resulting in tissue hypoxia.
-Pulmonary arterioles vasoconstrict in response to low O2 levels (in contrast to systemic arterioles which dilate in response to hypoxia.
-Vasoconstriction of pulmonary arterioles will increase pulmonary vascular resistance, and cause pulmonary hypertension (increased pulmonary artery pressure).
Decreases in tissue O2 levels within the lung cause pulmonary arteriolar vasoconstriction. Low O2 levels can occur in a variety of ways, including impaired ventilation, pulmonary edema, or living at high altitude.
If alveoli in an area of the lung have a low O2 level, arterioles in that area will constrict.
Since a major function of the lung is to oxygenate blood, this hypoxic pulmonary vasoconstriction will shift blood flow from poorly ventilated areas (low O2 levels) to well-ventilated areas of the lung. This characteristic is important in matching ventilation and perfusion in the lung.
If a person has left-sided heart failure, pulmonary venous pressure will be elevated and pulmonary edema will develop, resulting in generalized pulmonary arteriolar constriction. This will increase pulmonary vascular resistance and elevate pulmonary artery pressure. A chronic increase in afterload to the right ventricle will result in right ventricular hypertrophy. Chronic pulmonary hypertension can result in right heart failure. |
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Term
What are the common clinical signs in Left-sided heart failure?
Why would lying down lead to paroxysmal nocturnal dyspnea? |
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Definition
1. Dyspnea (difficulty breathing)
2. Orthopnea (sensation of labored breathing while lying down, and which is relieved by sitting up)
3. Paroxysmal nocturnal dyspnea (severe breathlessness that awakens person 2-3 hours after lying down to sleep)
These breathing problems are related to the development of pulmonary edema.
Why would laying down lead to paroxysmal nocturnal dyspnea?
-Starling's Law of the heart states that stroke volume increases when preload is increased.
-When a person lays down, venous return to the heart increases (gravity is no longer causing pooling of blood in the veins of the legs as when the person was standing).
-In a person with left-sided heart failure, lying down would promote pulmonary edema by increasing pulmonary venous pressure. This will increase pulmonary capillary pressure, increasing filtration.
-The increased venous return upon lying down will increase the likelihood that the person will experience orthopnea and paroxysmal nocturnal dyspnea.
Increased in venous return when you lie down. Which will increase filling of L ventricle. Which will raise pressure in the atria, which will increase pressure in the lungs leading to pulmonary edema even more. |
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Term
What is the BAROREFLEX RESPONSES TO DECREASED MAP DUE TO REDUCED CARDIAC OUTPUT?
Would increasing SYM firing be effective in someone with Systolic dysfunction?
What would afterload look like in heart failure? |
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Definition
Increased SYM firing will activate:
-beta-1 receptors which increases HR and SV (increased inotropic state)
-alpha-1 receptors which causes arteriolar constriction (increased TPR; major response) and venoconstriction (increased venous return).
-Decreased PARA firing will increase HR.
Increased SYM firing may not be very effective in increasing inotropic state in someone with systolic dysfunction.
-In this situation, the major baroreflex compensation will be increased TPR due to constriction of systemic arterioles (due to alpha-1 receptor activation by norepinephrine).
A consequence of increased TPR will be higher diastolic pressure in systemic arteries (due to a slower rate of runoff of blood from systemic arteries to veins).
As a result, afterload will be increased to the failing heart, which will further promote the progression of heart failure. One reason is that increased afterload (and increased heart rate) will increase myocardial O2 demand. |
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Term
| What is the neurohormonal activation via the baroreflex look like in someone with Low arterial pressure? |
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Definition
Neurohormonal activation via the baroreflex in response to low arterial pressure involves the following systems:
A. renin-angiotensin system
B. ADH release
C. adrenergic nervous system through the baroreflex
Although the acute effects of these systems are beneficial (compensatory responses to raise mean arterial pressure), chronic activation of these systems can ultimately be detrimental to the failing heart. |
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Term
| What is the mechanism in the Renin-Angiotensin system for increasing blood volume? How will this negatively affect a person? |
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Definition
Renin-Angiotensin System:
-Decreased mean arterial pressure will increase renin release from the kidney.
Plasma angiotensin II levels will be increased which will:
A. Cause constriction of vascular smooth muscle (increase TPR)
B. Stimulate ventricular myocyte growth (hypertrophy)
C. Increase aldosterone release from the adrenal gland
Increased circulating aldosterone will promote sodium and water reabsorption from the kidney.
This results in increased blood volume which will increase the severity of edema. |
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Term
| What would antidiuretic hormone do in patients with a decreased MAP? |
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Definition
Decreased mean arterial pressure will increase release of anti-diuretic hormone (ADH).
Higher circulating levels of ADH will decrease excretion of water by the kidney and increase blood volume.
The increased blood volume will increase ventricular end diastolic pressure and venous pressure, which will increase the severity of edema. |
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Term
| What will happen in chronic sympathetic stimulation in patients with a decreased MAP? |
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Definition
The decrease in mean arterial pressure in heart failure results in increased sympathetic nerve activity (and decreased parasympathetic nerve activity) via the baroreflex.
Chronic sympathetic stimulation of the heart results in down regulation of cardiac beta-adrenergic receptors (beta-1 receptors).
This response further decreases the inotropic state of the heart (lowering cardiac output) and decreases the sensitivity of the heart to catecholamines. |
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Term
CHRONIC BETA ADRENERGIC STIMULATION PROMOTES MYOCYTE DEATH, how?
CHRONIC BETA ADRENERGIC STIMULATION INCREASES CYTOSOLIC CALCIUM LEVELS DURING DIASTOLE, how? |
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Definition
1) In heart failure, beta adrenergic stimulation of the heart can result in CASPASE activation, causing myocyte cell death via necrosis and apoptosis. The loss of myocytes would contribute to development of systolic dysfunction.
2) In heart failure, beta adrenergic stimulation of the heart can also cause oxidative stress (through generation of reactive oxygen metabolite, ROS) within myocytes, which will result in leakage of calcium from the sarcoplasmic reticulum (SR). This leakage will increase cytosolic calcium during diastole, which will contribute to development of diastolic dysfunction. |
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Term
| What is the difference between pulmonary Edema vs shock? |
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Definition
If blood volume is too high in a person with left-sided heart failure, pulmonary edema will result.
If blood volume is reduced with a diuretic, stroke volume (and therefore cardiac output) will be reduced.
The goal is to reduce blood volume sufficiently to prevent pulmonary edema without reducing stroke volume (and cardiac output). |
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Term
Some patients with heart failure have down-regulation of cardiac beta-1 receptors (due to chronic stimulation of the heart by sympathetic nerves).
As a result in this group of patients, it is not possible to signficantly increase cardiac output by increasing inotropic state with catecholamines.
Based on Starling’s Law of the heart, how could stroke volume be increased in these patients? |
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Definition
Stroke volume is increased by:
1. an increase in preload (end diastolic volume)
2. a decrease in afterload (resistance to ejection)
3. an increase in inotropic state
ACE inhibitors have two beneficial effects in patients with heart failure:
1. Decreased afterload due to lower plasma angiotensin II levels (TPR will be decreased). This increases stroke volume by shifting the Starling curve upwards.
2. Decreased blood volume due to lower plasma aldosterone levels. This reduces end diastolic volume and decreases the likelihood of pulmonary edema. |
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Term
| What is the coronary blood flow during diastole? |
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Definition
Coronary blood flow is very low during systole and highest during diastole.
Approximately 80% of blood flow to the left ventricle occurs during diastole.
Aortic diastolic pressure will be decreased when afterload is reduced by ACE inhibitors.
If the decrease in aortic diastolic pressure is too great, myocardial ischemia could become more severe in someone with left heart failure. |
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Term
| What does Phenylephrine (alpha-1 agonist) do? |
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Definition
1. Direct effect:
A. constriction of vascular smooth muscle
- ↑ TPR due to arteriolar constriction (major effect)
- ↑ venous return due to venoconstriction
2. ↑ MAP
3. Baroreflex:
- ↓ SYM, ↑ PARA
- ↓ CO
Note:
Alpha 1 - increase TPR by constricting Arterioles. It will also constrict veins, which will promote filing of the heart. Changes in TPR in arterioles is much stronger than veins constriction.
Product of baroreceptor is decrease sym, increase para, decrease co.
Stroke volume would be decrease |
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Term
What does Isoproterenol (Non-selective beta agonist) do?
Isoproterenol is a Non-selective Beta Agonist, meaning it affects both Beta-1 and Beta 2 |
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Definition
IF PRIMARILY BETA-1 ACTIVATION IN HEART:
1. Direct effect:
A. if predominately activation of β1 receptors in heart
- ↑ CO due to ↑ HR
- and ↑ inotropic state (↑ SV)
2. ↑ MAP
3. Baroreflex:
A. ↓ SYM, ↑ PARA
-↓ TPR due to arteriolar dilation (major effect)
- venodilation lowers venous return and therefore SV
IF PRIMARILY BETA-2 ACTIVATION IN HEART:
1. Direct effect:
A. if predominately activation of β2 receptors in skeletal muscle arterioles:
- ↓ TPR
2. ↓ MAP
3. Baroreflex:
A. ↑ SYM, ↓ PARA
- ↑ CO due to ↑ HR
- and ↑ inotropic state (↑ SV) |
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Term
| What is the effect of Carotid Occlusion? |
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Definition
1. Direct effect:
A. clamps applied to carotid artery lower the blood pressure at the carotid baroreceptors
B. ↓ carotid baroreceptor firing, you get increased SYM and decrease para. This will lead to increasing TPR and CO (increased SV and HR)
2. ↑ MAP through baroreflex responses |
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Term
| What is the effect of Carotid Massage? |
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Definition
1. Direct effect:
A. external pressure applied to carotid arteries results in stretch of carotid baroreceptors
B. this "mimics" high pressure at carotid body
C. ↑ carotid baroreceptor firing, so you get a decrease in SYM and increased in PARA, resulting in decrease TPR, decreased in CO (decrease in SV and HR)
2.↓ MAP through baroreflex responses |
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Term
| What is the effect of Nitroglycerine? |
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Definition
1. Direct effect:
A. vascular smooth muscle relaxation
- ↓ TPR (major effect)
- ↓ venous return due to venodilation
2. ↓ MAP
3. Baroreflex:
A. ↑ SYM, ↓ PARA
- ↑ CO due to ↑ HR
- and ↑ inotropic state (↑ SV) |
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Term
| What happens during Vagal Stimulation? |
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Definition
Right Vagal Stimulation:
-Right vagus primarily innervates SA node.
-Sinus Bradycardia (due to mild stimulation)
-Complete inhibition of SA node firing (strong stimulation)
Left Vagal Nerve Stimulation:
-Left Vagus primarily innervates AV node
-1st or 2nd degree AV block (mild to moderate stimulation)
-3rd degree AV block (strong stimulation) |
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Term
| What is the baroreflex compensation to hemorrhagic shock? |
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Definition
Hemorrhagic leads to:
- decrease in CO,
-decrease in MAP,
- decrease firing of baroreceptor in Carotid arteries and Aorta
(Afferent Path) sends message to cardiovascular center in brain.
(Efferent Paths) increase SYM firing and decrease PARA firing.
-constriction of systemic arterioles leading to INCREASING TPR
-increase contractility force of heart and increase HR, RAISING CO
Ultimately, raises MAP toward normal. |
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Term
What is the BAROREFLEX COMPENSATIONS TO DISTRIBUTIVE SHOCK
(SEPTIC, ANAPHYLACTIC AND NEUROGENIC SHOCK) |
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Definition
In distributive shock, we get:
-decrease in TPR
-decreased in MAP
-decreased firing of baroreceptors in carotid arteries and Aorta
(Afferent path) signals to the cardiovascular center in brain
(Efferent path) – increase SYM and decrease PARA firing
-increase contractility force of heart and increase HR, INCREASING CO
-constriction of systemic arterioles RAISING TPR
Ultimately, raises MAP toward normal. |
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