Cardiovascular system Flashcards
Series/Parallel Connections
Intestinal circulation passes through the liver before returning to the atrium; glomerular circulation passes through the kidney tubules before returning to the atrium
Healthy levels for cardiac output
70kg woman, 5 liters/min at rest (5 total liters)
Total blood location
85% in the systemic circulation
75% of that in the venous circulation (65% of total)
Capacitive veins
those major veins who hold a great deal of the blood in the body; stretchy walls
Central blood volumes
all the blood in the thorax ~15%; vena cava, heart, aorta and pulmonary circulation
Blood in high pressure compartments
~15% of total blood (ventricles and large arteries)
Blood in pulmonary circulation
~10%
Blood in heart chambers
~5%
Poiseuille’s law
Flow = (P2-P1) * r^4/length
Factors affecting viscosity of blood
hematocrit (percentage of blood made up of RBC) and deformability of RBC’s (tendency to aggregate)
Dicrotic pressure wave
increased pressure in the aorta after the aortic valve closes
Incisura
When aortic pressure stops falling as the aortic valve is closed
Positive inotropic effect
increase in cardiac stroke volume (opposite for negative)
Methods for studying heart
1) Isolated Perfused Heart (take it out and cannulate the main vessels)
2) Isolated Superfused muscle - isolated muscle strips (or papillary muscle) studied in a petri dish
3) Patch clamp of isolated myocyte: isolate cells by digesting away the remainder with proteases. Attach patch clamp to study electrical impulses across the membrane (control cytoplasm)
Syncytium
groups of cells becoming one cell (algae e.g.)
Connexins/gap junctions
link the cytoplasm of neighboring cells together so that they effectively function as a unit (e.g. cardiac muscle)
Functional syncytium
cardiac muscle functions as a single unit, ergo it is a functional syncytium
Hemi-channels
half of the connexin formed by each myocyte; six subunit proteins form channel; max. diameter allows passage of 700 daltons molecule
intercalated discs
lines where the hemi-channels fuse to form the connexins which make the cardiac muscle a functional syncytium
Gap junctions/connexins close when
cytoplasmic Ca or H concentration becomes too high
What other organ has high connexin content?
Liver
Prevention of heart tetany
prolonger depolarization: 250 ms
absolute refractory period: during the action potential plateau, further stimulus has no effect
relative refractory period: after repolarization, stimulus has limited effect due to SR Ca release being limited
modulation of contractile force in the heart
caused by altering the transient Ca level released by the myocytes (can be altered by catecholamines)
Drugs that block Ca channels (heart)
dihydropyridines (L-type calcium channel blockers - used in treatment of hypertension)
Drugs that inhibit Na/K pumps (causing cytoplasmic Na to rise - causing transient Ca to rise)
heart glycoside (ouabain & strophantidin) - ((from Somalian waabaayo “arrow poison” - just a cool fact from wikipedia, not on the exam))
Difference between high vs. low concentrations of transient Ca drugs
high concentrations of ouabains or dihydropyridines will cause the heart to stop or to beat with great force, but used in lower concentrations they can have a different effect
L-type calcium channels
smooth and cardiac muscle calcium channels, open for a ‘long’ time
Nifedipine
developed by Bayer, dihydropyridine. Due to receptor uptake rate, it has a much greater effect on smooth muscle relaxation than it does on inotropic effect
Ouabain
when administered appropriately, intracellular Na should rise from about 7 mM to about 10-12 mM
Sequence of events heart contraction
1) AP upstroke due to Na depolarization
2) NCX and L-Type Ca Channel let Ca in
3) intracellular Ca increase causes more Ca release via ryanodine receptors (from SR)
5) transient Ca lowered by SERCA uptake back into SR
Percentage of Ca from L-type Ca Channel
10-25%
NCX
exchanges 3 Na for 1 Ca (3+ to 2+), works against the electrical gradient, bringing Ca in when the polarity across the membrane is positive; increases in cytoplasmic Na strongly interfere with Ca extrusion via the electrical gradient
differences between skeletal and cardiac muscle
decreases in extracellular Na increase the force of contraction of cardiac muscle: NCX pump can more effectively pump Ca into the cell
inversely increases in intracellular Na increase the force of contraction
Contracture
failure of the NCX to extrude Ca due to high levels of intracellular Na ‘Ca overload’
Ryanodine (cardio)
provokes contracture in skeletal muscle by releasing stores of intracellular Ca; NCX in heart can remove excess Ca though, making ryanodine a powerful negative inotrope
SR Ca pump (cardio) (PMCA)
P type pump; 2 Ca per ATP; handles 75-90% of transient Ca (NCX does the rest) PMCA
Na/K pump (in cardio) (NHE1)
provides the gradient for AP and for the NCX and NHE1
Calcium regulation of myocyte homeostasis
calcium levels are important for regulation of transcription and oxidative phosphorylation/glycolysis in myocytes (mitochondria have channel uptake and NCX removal system)
Frank-Starling Mechanism
stretching by 10-15% increases force of contracture by increasing ‘passive’ contracture; more fill = more powerful contracture
Titan
giant protein that is responsible for the stiffness of the passive tension of cardiac muscle; resists stretching past 2.2 microns; linked to Z-bands
Vmax of heart contraction
defined as the speed of cardiac muscle contraction when there is no “load,” which is to say blood to be pumped
Velocity (Cardiac output) vs. afterload
as afterload increases, the cardiac output (and the proportional velocity of cardiac muscle contraction) decreases. The work done by the heart can then increase, but this makes the heart less efficient
Frank-Starling Revisited (effects of increased preload)
Increased contraction of the heart following increased preload (due to stretching) causes end systolic volume to be similar regardless of the end diastolic volume
Effects of increased afterload
The stroke volume is forced to decrease (pushing against higher pressure), causing end systolic volume to increase (more left in the heart since it cannot pump as well)
Effects of increased contractility (ouabain)
End systolic volume is decreased (more powerful pump = less left in the reservoir)
Extrasystolic beats
when the cardiac release mechanism of Ca haven’t fully recovered from inactivation
Delayed beats
delayed beats have extra contractile force
Post extra-systolic potentiation
several extra beats occur, which do not release SR Ca. This builds up the amount of SR Ca leading to a potentiated beat that is extra powerful
frequency inotropy/treppe/Bowditch staircase
as the heart beats faster, the initial few beats are low contractile force beats, but the heart is able to reset to the new higher steady state and beat at normal contractile force
mechanism of frequency inotropy
intracellular concentrations of Na go up and therefore the NCX is less able to extrude Ca; as the Ca levels rise, the contractions increase
Anrep effect
contractility is improved by the heart in response to an increase in preload or afterload; temporary (1-2 mins) and thought to be caused by angiotensin II release from myocytes
