Cardiovascular Systems Physiology and Pathophysiology Flashcards
Describe the vasculature that blood passes through as it leaves the heart
Heart (oxygenated blood) —> arteries —> arterioles —> capillary beds (gas exchange) —> venules (deoxygenated blood) —> veins —> SVC and IVC
What are the component of the microcirculation of blood?
Arterioles, capillaries, and venules
The vena cava empty mixed venous blood (i.e.
deoxygenated blood from the superior and inferior circulatory beds) into the
Right atrium of the heart
At any given moment in time, most of our blood is in the
Venous system
Sequential blood flow through the central cardiovascular system during one complete cardiac
cycle is as follows:
Right atrium —> tricuspid valve —> right ventricle —> pulmonic semilunar valve —> pulmonary arteries (Deoxy) —> lungs —> pulmonary veins (Oxy) —> left atrium —> bicuspid valve —> left ventricle —> aortic semilunar valve —> aortic arch —> aorta —> arteries
The heart functions as two pumps in series which allow for which two types of circulations?
- ) Pulmonary circuolation (Exchange of CO2 for O2)
2. ) Systemic circulation (exchange of O2 for CO2)
In general, two phases of the cardiac pump occur and are defined by the properties of the ventricles. They are:
- ) Diastole: Ventriclular relaxation (low intraventricular pressure)
- ) Systole: Ventricular contraction (high intraventricular pressure)
Cardiac muscle is known as
Myocardium
Comprise the major portion of the ventricles by volume, however occupy only 25-30% by number
Cardiomyocytes (or just myocytes)
The heart beats on average around 100,000 beats per day to circulate around 6 tons of blood per day. This is a metabolically expensive process that uses approximately
6 kg of ATP daily
The substrate for all of this comes predominantly from
- ) Glucose (glycolysis)
2. ) Free fatty acids (FFA β-oxidation)
Glucose and free fatty acids feed into oxidative phosphorylation for generation of
ATP
In a healthy adult, approximately 60% of ATP is derived from
FFA β-oxidation
Under conditions of stress (e.g., heart failure or ischemia), a shift occurs resulting in proportionally more ATP being generated from
Glucose oxidation
This metabolic shift is important when you consider that glucose oxidation yields around
13% ATP per O2 molecule consumed than FFA β-oxidation
The use of FFA for energy in the heart is energetically wasteful because FFA stimulate the synthesis of
Mitochondrial uncoupling proteins
-releases heat instead of ATP
Collectively, the stressinduced shift from the β-oxidation of FFA to the oxidation of glucose results in the production of approximately
40% more ATP per O2 molecule
Which has a thinner myocardium, atria or ventricles?
Atria
What are the cells of the myocardium called?
Myocytes
Contraction of the myocyte operates via the sliding filament model that depends on
Ca2+ and ATP-dependent cross bridge cycling
The contractile element of the myocyte is referred to as the
Sarcomere
Intercalated disks form the end borders between myocyte fibers; and the fibers are separated laterally by the
Plasma membrane-like Sarcolemma
Cardiac muscle resembles a syncytium in that each fiber contains multiple nuclei; i.e. cardiac muscle fibers operate as a
Functional syncytium
Cardiac muscle cells and fibers are joined by
Gap junctions
Enable a high degree of electrical conductivity as well
as the free diffusion of very small molecules such as ions and some second messengers between cells
Gap junctions
Cardiac myocytes utilize oxidative phosphorylation for the production of ATP; thus, the cells are rich in
Mitochondria
Intracellular Ca2+ sinks that cab bolster sarcoplasmic Ca2+ concentrations
Mitochondria
An isoform of creatine kinase that is referred to as cardiac-specific CK
Creatine kinase MB (CK-MB)
What is the clinical importance of CK-MB?
CK-MB is dumped following a myocardial infarcation
How many hours from a myocardial infarction do we see:
- ) Rise of CK-MB
- ) Peak of CK-MB
- ) Return to normal CK-MB
- ) 3-8 hours
- ) 24 hours
- ) 48-72 hours
Since there are other CK isoforms, the ratio of CK-MB: total CK is measured. A reliable marker for myocardial injury is CK-MB : Total CK ratio of
> 2.5%
Cardiac muscle contains a T-tubule network as well as an abundant representation of
Sarcoplasmic reticulum (SR)
Cardiac muscle fibers are well vascularized, such that we have what type of correlation between capillaries and mucle fibers?
One capillary per muscle fiber
Like skeletal muscle, cardiac sarcomeres contain Z discs (Z lines) that anchor
Actin filaments
Like creatine kinases, there are specific cardiac
troponins. These are
- ) Cardiac troponin 1 (cTn1)
2. ) Cardiac troponin T (cTnT)
In the event of a myocardial infarction, cTn1 and cTnT will both rise. When will we see their
- ) Rise
- ) Peak
- ) Return to normal
- ) 3-4 hours post infarction
- ) 18-36 hours post infarction
- ) 10-14 days post infarction
What is the current gold standard for diagnosis of a myocardial injury?
Measurement of the cardiac troponins
Cardiac muscle fibers are strongest at the
Onset of contraction (from approximately L0)
Unlike skeletal muscle, we see a greater contractile force when cardiac muscle is
Stretched
This is because unlike skeletal muscle, a very slight stretch from L0 is one signal to the cardiomyocyte to
Release intracellular Ca2+ from SR and mitochondria
With increase intracellular Ca2+ comes
Increased contractile force
When compared to other muscle types, cardiac muscle can develop much more tension from
Stretch
Represents the phase following the ejection of blood from the left ventricle (LV)
Beinning of diastole
Diastole is considered the relaxed (resting) stage; hence the LV fibers have essentially no
Load
During diastole the
- ) Aortic valve is
- ) Mirtal valve is
- ) Closed
2. ) Open
During early diastole, the mitral valve opens in response to an
Increasing LA pressure (from filling) and low LV pressure
-When mitral valve opens, LV begins to fill
The atria contract in response to SA nodal firing;
this represents the later stage of
Ventricular diastole
Only about 20% of ventricular filling is due to
Atrial systole
Filling causes preload on the LV muscle fibers. In other words, preload is caused by blood induced filling that causes
Stretch from L0
What is laplaces law for the left ventricle?
T = P x r
Wall tension = Pressure x radius
Therefore, greater chamber wall tensions are experienced with greater filling, and increased wall tension upregulates
Oxygen demand
As the LV muscle fibers are stretched to the optimal length, intracellular Ca2+ is increased and systole begins; this early systolic phase is specifically referred to as
Isovolumetric contraction
The optimal myosin cross-bridge/actin overlap is referred to as the
Optimal length
Contraction of cardiomyocytes depends upon Na+ stimulated AP that in turn activates
Voltage-dependent Ca2+ channels
What happens during isovolumetric contraction?
Mitral and aortic valves are closed and LV pressure (LVP) soars
As isovolumetric contraction proceeds, the resistance of aortic blood pressure against LVP is added, and this opposing aortic pressure is known as
Afterload
What must happen in order for the LV to empty efficiently?
Preload must be greater than afterload
As the force of isovolumetric contraction exceeds afterload, the aortic semilunar valve is pushed open, the LV ejects blood into the aorta, and
Systolic contraction of the LV terminates
When arterial blood pressure is increased, the heart has to work even harder to eject blood from the LV. This is the case often seen with
Hypertension
In cardiac muscle, how do we represent
- ) Stress
- ) Length
- ) Pressure
2. ) Volume
The relationship between volume and pressure seen in the heart are referred to as the
Frank-Starling Laws
Explains what happens to the stress (pressure) in a cardiac cycle?
Minimum stress exists at L0. Then as the chamber fills (increased LVV during diastole) a slight stretch from L0 is initiated and from the onset of isovolumetric contraction, we see an exponential increase in the rise of stress (pressure). Then, as contraction proceeds (chamber emptying, systole) and blood is ejected, the rate of rise of pressure (stress) slows, peaks, and begins a rapid exponential decline and returns to near zero at the end of systole
The pressure-volume plot shows these relationships during one cardiac cycle and reads sequentially from
Left to right, then bottom to top, then right to left, then top to bottom
Phase 1 of the pressure-volume plot represents
Diastolic filling and generation of preload
The difference between the beginning of isovolumetric relaxation and end diastolic volume (EDV) represents the
Stroke volume (SV)
Phase 2 of the pressure-volume plot represents
The isovolumetric contraction stage of systole
Phase 3 of the pressure-volume plot represents
Systolic ejection
Phase 4 of the pressure-volume plot represents
Isovolumetric relaxation
Represent the maximal ventricular pressure developed at a given inotropic state
The end systolic pressure-volume (ESPVR) plots
What are the effects of an increased end diastolic volume (EDV)?
Increased preload, increased systolic intraventricular pressure (IVP), and slightly increased end systolic volume (ESV)
Will increase both systolic IVP and ESV and result in a greater ESV than increased preload
Increased afterload
How does positive inotropy change the pressure-volume relationship?
Reduced ESV (from greater systolic ejection) and increased stroke volume
What is phase 1 of a velocity of fiber shortening vs LVV?
Muscle fiber velocity is 0, ventricular myocardium is relaxing
What is phase 2 of a velocity of fiber shortening vs LVV?
Isovolumetric contraction that terminates upon aortic valce opening
Myocyte tension rises dramatically during
Isovolumetric contraction
Myocyte tension rises dramatically during isovolumetric contraction. This provides the generation of force that is required to
Overcome afterload and push open aortic valve
The rapid decline in muscle fiber shortening during phase 3 represents
Systole
The velocity of muscle fibers shortening precipitously declines during
Systole
Increased afterload is translated as an opposing force that results in a
Robust decrease in contractile velocity and increase in ESV
Abnormally increased preload causes a
Slight decrease in contractile velocity and a concomitant increase in ESV
Why does an abnormally increased preload cause a slight decrease in contractile velocity?
Because the fibers are stretched beyond optimal length for myosin-actin overlap
Naturally occurring and pharmacologic factors that can alter the force of cardiac muscle contractility
Inotropic compounds
What 4 things do positive inotropins increase?
- ) Ventricular contractile force
- ) EDV
- ) Contractile velocity
- ) May or may not alter time between excitation episodes
Thus, a positive inotropin such as adrenergics or digitalis may increase
-as long as HR does not increase such that the time required for ventricular filling is compromised
Cardiac output
The goal of positive inotropic compounds is to increase
Cardiac pumping efficiency
Contraction of cardiac muscle is dependent upon APs induced by
Na+ influx
Contraction of cardiac muscle is dependent upon APs induced by Na+ influx, and contraction results from (and depends upon)
Increased sacoplasmic Ca2+
Prolongs the duration of contraction, thus lengthening the QT interval within the electrocardiogram (ECG)
Hypocalcemia
Reduces the duration of contraction, and thereby shortens the QT interval
Hypercalcemia
The effects of abnormally high or low calcium on QT involve allosteric modulation by calcium on the voltage-gated Na+ channels which control
Ventricular myocyte depolarization
Abnormally low extracellular calcium (hypocalcemia) tends to cause a rapid
Activation-inactivation of these Na+ channels
A cardiac glycoside; this drug that inhibits the Na+/K+ ATPase within the cardiomyocytes, this results in increased intracellular Na+
Digoxin
Elevated intracellular Na+ impedes the
Na+/Ca2+ exchanger (NCX)
Trades Na+ import for Ca2+ export from cardiomycetes
NCX
What are the effects of impeding the NCX?
Intracellular Ca2+ increaes, thus enhancing contraction
Thus, Digoxin exerts what type of inotropic effect?
Positive inotropic effect
Digoxin is also a vagomimetic agent, meaning it
Slows SA and AV conduction and sensitizes broreceptors
Increases afferent inhibitory activity which reduces activation of the sympathetic nervous system (SNS) afferents which up-regulate heart rate and vasoconstriction
Digoxins effect on baroreceptors
