Lecture 1 Flashcards
Effective circulating volume (ECV) =
- volume sensed by baroreceptor system which is available for perfusion.
Primary energy source of the heart
(non-stress scenario):
- Free fatty acid
- β-oxidation
- oxidative phosphorylation
- ATP
Secondary energy source of the heart
(stress scenario):
- Glucose
- Glycolysis
- Oxidative phosphorylation
- ATP
Heart source of energy in non-stress and in stress:
- Non-stress: Free fatty acids
- Stress: Glucose
The predominant differences between cardiac muscle and skeletal muscle:
-
cardiac muscle has:
- chronic work load
- high reliance on extracellular calcium
Type of calcium channels expressed in cardiac myocytes:
-
Type-L calcium channels.
- Calcium enters myocytes through these channels to allow for cross-bridge cycling/contraction.
The two pathways in which an action potential in the heart can cause an influx of calcium into the sarcolemma of a myocyte:
- Extracellular: Type L Ca2+ channels
- Intracellular: T-tubules (DHPR and RyR)
The two sources of calcium for cardiac myocytes:
- Extracellular:
- enter sarcolemma via Type-L Ca2+ channels.
- Intracellular:
- enter sarcolemma via T-tubules (DHPRs and RyRs).
Phospholamban:
- protein phosphorylated by PKA.
- Unphosphorylated state: inhibits SERCA.
- Phosphorylated state: SERCA activated.
Process of cardiomyocyte relaxation:
- Phospholamban phosphorylated; SERCA channels activated.
- Calcium efflux via SERCA channels and NCX ATPases.
What two structures are utilized by cardiomyocytes to cause calcium efflux from the sarcolemma and relaxation?
- SERCA channels
- NCX ATPase
- secondary active transporter
- sodium-calcium exchanger
Creatinine kinase function:
- enzyme
- converts creatine to phosphocreatine and ADP.
- phosphocreatine + ADP = ATP.
Creatinine kinase expressed in myocardium:
CK-MB; “cardiac-specific CK.”
- rises beginning around 3-8 h post-injury.
- returns to normal within 48-72 h post-injury.
Troponins expressed in myocardium:
cTnI and cTnT
- cardiac troponin I (cTnI)
- cardiac troponin T (cTnT)
- rise within around 3-4 h post-injury.
- return to normal over 10-14 d post-injury.
What cardiac-specific markers increase in blood plasma levels post-myocardium injury?
- CK-MB (creatinine kinase)
- cTnI (cardiac troponin I)
- cTnT (cardiac troponin T)
Diastole characteristics (4):
- Phase of ventricular filling
- Myocardium relaxed
- Low intraventricular pressure
- Lowest arterial BP
The two values associated with diastole:
- End diastolic pressure (EDP)
- End diastolic volume (EDV)
Systole characteristics (4):
- Phase of ventricular emptying
- Myocardium contracting
- Highest intraventricular pressure
- Highest arterial BP
The two values associated with systole:
- End systolic pressure (ESP)
- End systolic volume (ESV)
When does the lowest arterial BP occur?
diastole
When does the highest arterial BP occur?
systole
Cardiac output (CO) =
CO = SV X HR
- (stroke volume X heart rate)
- SV = EDV - ESV
Stroke volume (SV) =
SV = EDV - ESV
(end diastolic volume - end systolic volume)
What are end diastolic volume (EDV) and end systolic volume (ESV)?
- EDV = left ventricle volume after diastole (filling).
- ESV = left ventricle volume after systole (emptying).
- SV = EDV - ESV
Mean arterial pressure (MAP) =
MAP = CO x TPR
(TPR = total peripheral resistance)
Mean arterial pressure (MAP) represents the:
- perfusion pressure; the driving force to maintain tissue perfusion (i.e. oxygenation).
Cardiac output (CO) must be equal to:
- venous return.
- What goes out of the heart at the left ventricle must come back into the heart at the right atrium.
What is occuring if cardiac output (CO) does not equal venous return?
either losing blood or edema.
Right atrial pressure (RAP)/central venous pressure (CVP):
- pressure in the right atrium due to venous return.
- lowest BP in body (0-2mm Hg).
Average values of RAP/CVP and MAP:
- RAP/CVP: 0-2mm Hg
- MAP: 80-100mm Hg
Functional important of the difference in MAP and RAP/CVP:
- creates a pressure gradient favoring venous return to right atrium and normal blood flow.
What will occur if RAP/CVP increases?
- venous return impaired.
- edema will manifest.
If output to the lungs via the pulmonary trunk/right ventricle does not equal the input into the left atrium via the pulmonary veins, what occurs?
pulmonary edema
What occurs to the atrium and ventricles during ventricular diastole?
- Atrial systole.
- Ventricular relaxation and chamber filling.
- Blood flows through tricuspid/mitral valves.
Normal ejection fraction (EF) percentage:
55-75%
Normal regurgitant fraction:
0
Ejection fraction (EF) =
EF = SV/EDV
(stroke volume/end diastolic volume)
The ejection fraction (EF) is:
- The fraction of blood from a given diastole that is ejected by the following systole.
- Normal: 55-75%.
In the heart, force = ?, and distance = ?
- force = pressure
- distance = Δvolume
Conditions required for the left ventricle to eject blood:
preload (LV pressure) > afterload (aortic pressure)
As the left ventricle begins to fill during diastole, what occurs to the cardiomyocytes?
- Begin to stretch. Passive tension develops.
- Stretch-induced calcium release. Influx of calcium.
Isovolumetric contraction of the left ventricle:
- Period in which left ventricle is contracting, but intraventricular pressure is less than aortic pressure. No movement of blood occurs.
- When left intraventricular pressure overcomes aortic pressure, aortic valve snaps open and ejection occurs.
Stretch-induced calcium release:
- When left ventricular myocytes get stretched out during diastole, they begin to experience an influx of calcium in addition to an increase in passive tension.
Afterload of the left ventricle and right ventricle, respectively:
- Left ventricle: aortic pressure.
- Right ventricle: pulmonary artery pressure.
After PKA is activated by some stimulus, what does it activate via phosphorylation (3)?
-
phospholamban
- activates SERCA
- relaxation
-
Troponin I
- dissociates calcium from tropononin C
- relaxation
-
Type-L calcium channels
- influx of extracellular calcium
- contraction
What does PKA phosphorylate in order to induce ventricular relaxation?
-
phospholamban
- activates SERCA
- relaxation
-
Troponin I
- dissociates calcium from tropononin C
- relaxation
What does PKA phosphorylate in order to induce ventricular contraction?
-
Type-L calcium channels
- influx of extracellular calcium
- contraction
Calcium efflux and influx are both happening at the same time due to PKA.
Whether or not contraction/relaxation occurs depends on:
- Whether calcium levels are above or below threshold required for contraction.
- Contraction occurs when the influx of calcium is greater than the efflux of calcium and above the required threshold for contraction.
How does epi/norepi increase HR (2)?
- activation/phosphorylation of PKA via β1 adrenoreceptors.
- increased rate of SA nodal firing.
NCX ATPase location and function:
- Sodium-calcium exchanger on sarcolemma of ventricular myocytes.
- Calcium efflux, sodium influx. RELAXATION.
- Secondary active transporter.
- Primary active transporter is Na+/K+ ATPase.
NCX ATPase is a secondary active trasnporter. What is its required primary active transporter?
Na+/K+ ATPase.
- Pumps sodium out.
- Sets up favorable concentration gradient for NCX ATPase.
What drug can inhibit Na+/K+ ATPase in ventricular myocytes, and what is the outcome?
Digitalis/digoxin.
- Sarcolemma calcium levels rise, increased cardiac output.
Digitalis/digoxin drug class and mechanism:
- Positive inotrope. Increases cardiac output.
- Inhibits Na+/K+ ATPase pump, reduces electrochemical driving force for NCX, sarcolemma calcium levels will rise, heart contracts harder.
