MSP PHYSIO PROBLEM SET #1
1) a. As capacitance vessels, veins contain the majority of blood volume at rest.
How does venular structure contribute to this property?
Answer: Not only do veins have a smaller wall thickness relative to
arteries, but they also contain less smooth muscle and more collagen in
comparison. As a result, veins are very compliant (“less stiff”) which
allows them to substantially increase their volume with an increase in
pressure. In other words, veins easily expand, thus serving as a reservoir
(or sink) for the vasculature’s blood.
b. During stress/exercise, autonomic regulation constricts veins. How does this
affect central venous pressure and the relative distribution of blood in the
vascular tree (i.e. relative volume in arterial vs. venous system)?
Answer: Upon constriction, the venous pressure increases and vessel
capacitance decreases, hence a portion of “storage” blood is now
distributed into the arterial system (for delivery to tissues).
(via increased preload)
2) One day while in his office, your preceptor (an internist) decides to test your
knowledge of cardiac physiology. He hands you a copy of the “wigger’s
diagram” and asks the followinga. “Immediately following S1, which valve opens first and why?”
Answer: A glance at the diagram shows that pulmonary artery pressure
begins to rise before aortic pressure, thus the pulmonary valve must open
first. Reason: the diastolic pressure in the pulmonary valve is smaller than
that of the aorta.
b. “A distinction is made between electrical systole and mechanical systole. Can
you show me which points on the diagram indicate the beginning of each? Also,
why don’t the electrical and mechanical events occur simultaneously?”
Answer: Electrical systole begins at the letter Q of the ECG, while
mechanical systole begins at the isovolumic contraction of the left
ventricle. These two events do not coincide for a number of reasons
including: a substantial number of cells must be depolarized for the
muscle to contract and; delta V must open voltage-dependent Ca channels
so that extracellular Ca will lead to release of sarcoplasmic reticulum Ca
(Ca-induced release of Ca) which will eventually bind to troponin and lead
to contraction.
c. “You’re doing very well, so this is the last question.” Suppose that a patient
presents with tricuspid insufficiency [due to strep endocarditis ]. Briefly describe
changes (if any) which would occur in the right atrial pressure trace?”
Answer: assuming there is no stenosis, the a wave should be the same.
The c wave will greatly diminish, but the v wave will become gigantic.
3.) Refer to the P-V loop in your notes for the following questions.
a. Write the equation for ejection fraction using letters on the diagram (e.g. E.F.
= cxa/b-d).
Answer: ejection fraction = b-d/b
b. According to the diagram, what is this person’s systolic and diastolic pressure?
Answer: Since rapid ejection begins at C, this is the diastolic pressure (80
mm Hg). Systolic pressure is equal to the max LV pressure of approx. 110
mm Hg.
c. Which letter is closest to the region of aortic valve closure?
Answer: The aortic valve closes as isovolumic relaxation begins which is
D.
3.
You’re talking to a patient who has recently had a heart transplant. The
patient relates, “I was warming up to go running during my lunch break when I
saw a group of devastatingly good looking students walking down the hall -I think their shirts and jackets said class of 2001 on them. So I notice that a
little later my heart starts beating faster, and things get worse when I start
running. My heart gets beating super fast, and I start feeling light-headed so I
have to stop. I can’t approach those second-year medical students, I get so
nervous, so I figured that you might know what’s going on.”
Answer: As HR increases, the time to fill the heart (diastole) decreases
more than systole. Because of Starling’s Law, the stroke volume
decreases. Also, a faster heart rate leads to a shift of blood from veins
to arteries, thus decreasing preload and increasing afterload – both of
which also contribute to a decreased stroke volume. At high enough
heart rates, the stroke volume is very low, as the heart has so little time
to fill. Cardiac output decreases, the patient feels light-headed as less
bloodflow gets to the brain.
4.
On your first preceptor visit after Christmas break, your preceptor’s office is
busier than the return/exchange lines the day after Christmas. While running
down the halls and almost out of breath, your preceptor quickly asks, “Are you
taking cardiac physiology yet?” You nod your head, and your preceptor says,
“Good. I gotta go to the bathroom – gotta cut back on the coffee -- but if you
could figure out this patient’s stroke volume before I get back, that’d be great.
All the information you need should be on the front page of the chart. Use the
Fick, Luke!” Before you can confess how little you’ve studied, your preceptor
is gone. You look at the patient’s chart and see:
Hb: 15 gm/dl x 1.36 ml O2 / gm Hb x 10 = 204 mL O2 / L blood
Pulmonary Vein O2 saturation:
95%
Pulmonary Artery O2 saturation: 60%
VO2 = 250 mL/min (Vo2 is a measure of O2 consumption)
HR = 100
You concentrate and hear “Use the Fick, Luke…” echoing in your head.
Your preceptor returns and says, “Well, my young jedi student doctor, what is
the patient’s stroke volume? You respond in your best Yoda voice:
Answer: Fick’s says that CO = VO2/ (arterial-venous O2 difference)
a-v difference = 204 mL O2/L blood (.95 - .6) = 71.4 mL O2/L blood
CO = (250 mL O2/min) / (71.4 mL O2/L blood) = 3.5 L/min
SV = CO/HR = (3.5L/min)/(100 min-1) = .035 L or 35mL
(normal stroke volume is ~ 75 mL)
also be prepared to discuss sampling sites for venous blood
Dissecting a pressure-volume curve
D
C
B
A
6) a. What sets the upper boundary of these loops (the upper dotted line)?
This line represents the Frank-Starling mechanism. It is set by the systolic
pressure that would be produced in a purely isovolumetric contraction
from a given end diastolic end-diastolic volume (EDV). The larger the EDV,
the greater the stretch of the ventricle and subsequently the greater the
tension and pressure which develops. A normal intact ventricle only
operates on the ascending limb of the length-tension curve.
b. What sets the lower border of the loops (lower dotted line)?
The lower border is set by the passive pressure-volume curve of the
relaxed ventricle.
c. Which of the four loops (A,B,C,D) represents the greatest stroke volume?
Stroke volume = EDV – ESV. It is represented by the width of the loop, thus
loop B reflects the greatest volume change.
d. What happened physically between loop A (the control state) and loop B?
Loop B shows the effect of increasing the end-diastolic volume; stroke volume
increases provided the arterial pressure (afterload) does not change.
e. What can cause the loop to change from B to C?
There is an increase in arterial pressure in loop C. The stroke volume
decreases, provided the EDV does not change.
f. How can you explain “loop” D?
Loop D depicts a purely isovolumetric contraction.
7) Considering all the free time you have in med school, you decide you want to
start marathon training. On one of those long training runs you start thinking
about your heart. You remember from physiology that your heart becomes more
efficient, and the "muscle pump" increases the return of the blood to your heart.
Describe the mechanism and effect of this increase .
The concept we are dealing with is increased preload. Increased blood
return to the heart increases the end diastolic pressure which causes
stretching of the myocardium. The stretched myocytes have increased
force of contraction. Maximum force of contraction develops at sarcomere
lengths of 2.2-2.3um. The sarcomere length of the heart at normal enddiastolic pressure is below this optimal value. Beyond 2.2-2.3 um the
contraction force decays, but it is difficult to stretch sarcomeres beyond
this point even in vitro. Part of the explanation is that at sarcomere lengths
below 2.0 um, the opposing actin filaments overlap each other or buckle
and this interferes with the formation of actin-myosin crossbridges. Also
important in cardiac muscle is the length-dependent calcium sensitivity.
The mechanism of this is unknown but experimentally it has been
measured that there is a substantial reduction in the calcium concentration
needed to produce 50% of maximal tension in the stretched heart. All
these concepts relate to Starling's Law of the heart, which simply states
that the greater the stretch of the ventricle in diastole, the greater the
stroke work achieved in systole.
8) At your preceptor's office you encounter a heavy set middle aged man who
complains that he loses his breath after climbing one flight of stairs, and it seems
to be getting worse. During the course of HEADS, you find that he smokes 50
pack years (2 packs a day for 25 years). In addition you find out that he enjoys
drinking a "couple" beers with his buddies after work, and then goes home and
has a "couple" more while eating fried chicken and watching TV. In addition, he
does not like doctors, and has not seen a physician since his discharge from the
Navy 15 years ago. After taking blood pressures all first semester, you expertly
find that his blood pressure is 200/120. Illustrate how this history will affect the
output of the heart.
1. This man has hypertension. Initially his high diastolic pressure
will lead to pathology. This man is feeling a huge afterload. The
ejection phase of the heart can only occur after the ventricular
pressure rises higher than the arterial diastolic pressure. Much of
the energy of the heart will be wasted in isometric contraction just
to reach pressures high enough to exceed the arterial pressure.
This will reduce the stroke volume and the ejection fraction of the
heart. Initially the body will maintain cardiac output by increasing
the heart rate. (this is about as much as the MSP students need
to know right now) Further information below.
2. The preload of the heart will increase in the chronic state due to
venoconstriction and the renin-angiotensin response which will
increase the blood return to the heart. The body increases the
volume in the heart because it wants to maintain stroke volume
so thinks just add more fluid. (They don’t need to know this yet,
but do they do need to know the effects of the increase preload.)
They should understand that increased preload will increase the
contractility of the heart (Starling’s Law) initially. In the chronic
state however the increase ventricular pressure will increase the
wall tension (Pressure in Law of Laplace). This will serve to
increase the oxygen consumption of the heart, reducing its
efficiency. Eventually this will overwhelm the heart muscle
causing the ventricle to dilate. Again this will increase the
oxygen demand of the heart (radius in Law of Laplace). Also this
will remodel the ventricle to a more spherical shape. Levick
points out that the more spherical shape of the heart reduces its
efficiency because a smaller component of the wall tension is
angled towards the cavity, generating less pressure. The
curvature of the ventricle wall determines how effectively the
active wall tension is converted into intraventricular pressure.
Why is this guy short of breath?
There are two reasons for his shortness of breath. The first, as discussed
above his stroke volume and cardiac output are diminished. This means
that he is not efficiently perfusing his working muscles. This man will feel
fatigue even after minimal exertion. Secondly, increased end diastolic
pressure in the left ventricle will back up and increase the end diastolic
pressure in the left atrium, which will back up into the pulmonary
capillaries causing pulmonary edema. As they will learn in respiratory
lectures (later), water in the longs decreases the efficiency of the gas
exchange, decreasing the oxygen saturation in the pulmonary veins.
9) Your good friend at USC medical school brags to you about his discovery of a
novel heart that lacks outer membrane calcium channels. He explains to you
how this definitively proves that all of the calcium needed for heart function is
present in the sarcomplasm reticulum. Defend or counter the credibility of such a
heart.
A heart like this could never exist. Our friend at USC is partly right most of
the calcium for cardiac myocyte contraction does come from the SR (8090%). However external calcium is integral in excitation-contraction
coupling. The plateau phase of the heart action potential is due to entry of
external calcium into the myocyte. Experimentally it has been shown that
the size of plateau currents directly affect the strength of contraction of the
cardiac myocytes. The externally derived calcium is integral in facilitating
calcium-induced calcium release of the much larger and more important
calcium store in the SR.
10) Explain how digoxin works in treating heart failure, given that it inhibits the
Na/K pump. Feel free to use diagrams and mention all the channels involved.
Digoxin is used to treat heart failure by enhancing the myocardial
contractile force. It achieves this by increasing the level of intracellular
calcium. Digoxin slows down the sarcolemmal Na/K pump by inhibiting its
ATPase activity. This produces a rise in intracellular sodium concentration
and a fall in the sodium gradient across the cell membrane. Since the
Na/Ca exchanger is driven by the sodium gradient calcium expulsion is
slowed and calcium accumulates in the cell. This increases the amount of
calcium available to bind to troponin for every excitation.
11) Draw the force curve for isometric contraction and explain the events
occurring between the actin and the myosin.
_____
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-------I tried to make it look like a flat curve as seen on page 21 of the Homsher
notes. Initially the crossbridge is detached in the bent confirmation with
ADP and Pi bound to it. Then the crossbridge collides with an interaction
site on the actin molecule and becomes strongly attached to the actin.
Then the Pi dissociates from the myosin head prompted by the
conformational change associated with the actin binding to the
crossbridge. Then a force is applied to the system (holding the barbell up
in the air). This causes the myosin neck to assume the straightened form
which stretches the S-2 segment. In isometric contraction the force
exerted by the S-2 segment to keep the sarcomere from increasing in
length by definition has to be equal to the force applied by the environment
on the sarcomere. The crossbridge may stay in this conformation for
several hundred ms. Then the ADP dissociates, the forms the plateau
phase of the force curve (the actin and myosin are still attached in the
extended neck form). ATP rapidly binds to the active site. Soon after ATP
binds to the catalytic site the crossbridge detaches from the actin and the
force between the thick and thin filaments falls to zero. Over the next 10-30
ms the crossbridge hydrolyzes the ATP returning the crossbridge
conformation back to the first step so that the cycle can resume.