Download SBPM SSN Short Answers #3 - Columbia University Medical Center

SBPM SSN Short Answers #3
Dec. 3, 2002
1. Draw the pressure – volume loop and label the following points:
End Systolic volume = C
End diastolic volume = A
Systolic Blood pressure = Highest point on curve (between points C and B)
End systolic pressure = C
Diastolic Blood pressure = B
End diastolic pressure = A
Left atrial pressure = D
Mitral valve closure = A
Mitral valve opening = D
Aortic valve opening = B
Aortic valve closure = C
2.Give three ways by which cardiac contractility could be decreased.
What feature of the cardiac PV loop is
the most reliable index of contractility?
A decrease in cardiac contractility could be due to:
1. A reduction in the amount of calcium released to the myofilaments
2. A reduction in the affinity of the myofilaments for calcium (e.g. a reduction in troponin’s affinity for
calcium)
3.
A reduction in the number of myofilaments available for contraction (e.g. a loss of heart cells because
of a myocardial infarct)
Pharmacological mechanisms for changing cardiac contractility work through the first two mechanisms.
For example, propanolol, a B-adrenergic antagonist, reduces the amount of calcium released to the
myofilaments and is therefore a negatively inotropic agent.
The most reliable index of contractility is the end-systolic elastance (Ees), the slope of the linear ESPVR.
The slope of this line is can be changed by the mechanisms described above.
The other two parameters that define the PV loop are V 0 (the volume-axis intercept of ESPVR) and the
EDPVR curve. Neither of these is significantly affected by changes in contractility. Other features of the PV
loop, such as stroke volume, can be manipulated without changing contractility, and therefore they too are not
good indices of contractility.
3.
Two interns are arguing about a patient who they suspect has abnormal His-Purkinje conduction. One
says that His-Purkinje conduction cannot be seen on EKG’s, the other says that there are things that can be
determined about His-Purkinje conduction on an EKG.
-Firstly, how do you set up an EKG on a pt? Just give me simplest one with the fewest leads and where they
need to be put.
One lead on each forearm and one on the left leg.
-Can His-Purkinje conduction be seen as a deflection on an EKG? What is the physical reason for your
answer?
No, the fibers are too few to cause a noticeable depolarization.
-Can you detect a His-Purkinje conduction abnormality on EKG? Why and how?
Yes, the time between the P wave and QRS complex tells you how long the elelctrical signal is in the His-Purkinje
fibers and too long is bad.
You disregard what the interns are arguing about and set up the EKG to find out about the patient for
yourself. You find that the patient is entirely missing one of the waves.
-Which wave is most likely missing in a patient who is walking, talking and relatively healthy?
P wave
-Describe a very common, not necessarily life threatening dysfunction in which this wave is missing. What
causes it, what is its physical manifestation and how does a healthy heart compensate for it (more specifically,
how does a healthy heart maintain adequate blood flow and give at least two parts which can help maintain
heart rhythm).
atrial fibrillation. caused by SA node firing too rapidly for atrial muscles to keep up
Atria no longer beat in synchronous fashion; they just quiver constantly
His-Purkinje fibers or ventricular muscle have intrinsic rhythm, which takes over
4. What effect does the autonomic nervous system have on the electrical activity of each of the following sites
in the heart?
Sympathetic Nervous System
Sinus Node
Pacemaker current activated at
more positive potentials,
increased inward pacemaker
current  increased rate of
initiation of pacemaker cells 
increased heart rate (positive
chronotropic)
Parasympathetic Nervous
System
Increased K+ conductance 
slows impulse initiation and heart
rate (negative chronotropic)
Atria
--------------------------------
Increased outward repolarizing
K+ current  shortens refractory
period of atrial cells  cells can
be excited more frequently
No effect under normal
conditions when sinus node
controls heart rate
AV Node
Norepinephrine increases inward
L-type Ca2+ current  increases
rate and amplitude of action
potentials  speeds conduction
of impulses through the AV node
(positive dromotropic)
Ach decreases inward L-type
Ca2+ current  slows rate of
depolarization & decreases
amplitude of action potential 
slows or stops conduction
through AV node
Decreased effective refractory
period
Ach delays removal of
inactivation from L-type Ca2+
current  longer effective
refractory period  decreased #
of impulses pass through node
Increased K+ conductance 
opposes depolarizing effect of Ltype Ca2+ current  slows
conduction
His-Purkinje
System/Ventricular
Muscle
Activation of pacemaker current
shifted in more positive direction
 current more fully activated
immediately after repolarization,
increased inward pacemaker
current  increased rate of
spontaneous depolarization
Inhibits sympathetic effects by
preventing release of
norepinephrine
No effect under normal
conditions when sinus node
controls heart rate
Increased L-type Ca2+ current 
increased contractile force of
ventricular muscle
5. At Thanksgiving dinner, your aunt Gilda looks up from her mashed potatoes and gravy to ask you, as the
new family medical expert, about her last visit to her doctor. Lately Gilda has been feeling a little lightheaded, and her doctor is concerned that she has developed athersclerosis in her carotid arteries. She’s a
little nervous about this and wants some free medical advice from her favorite niece/nephew.
After protesting that, hey, you’re just a first-year and you haven’t even dissected out the carotids yet in
anatomy lab, you tell her that you think she’s feeling light-headed because she’s not getting enough blood to
the brain! What are some of the mechanisms that regulate blood flow to a given part of the body?
There are four types of regulation of blood flow: 1) myogenic, 2) shear dependent, 3) metabolic, and 4) extrinsic.
Myogenic regulation refers to the ability of the vascular smooth muscle in blood vessel walls to relax or contract in
response to changes in blood pressure, maintaining a relatively steady flow. Shear-dependent regulation is the
vasodilation of arterioles and small arteries in response to increased shear, such as occurs with an increase in flow.
This is mediated by the release of nitric oxide from endothelial cells, which contain an inducible nitric oxide
synthase (nitric oxide synthases are discussed in more detail in the syllabus). Metabolic regulation is the
vasodilation of blood vessels in response to oxygen deprivation in the tissues, and is mediated by several substances.
Extrinsic regulation refers to the control of hemodynamic parameters by the autonomic nervous system.
Aunt Gilda is encouraged by your knowledge and continues complaining of aches and pains from head to toe,
including swelling in her ankles. What might be causing this?
The swollen ankles are edema, which occurs when more fluid accumulates in the interstitial space. This could be
caused by high hydrostatic pressure (hypertension) or by low oncotic pressure. In the microcirculation, four forces
govern the movement of fluid between the blood and the interstitial space: 1) hydrostatic pressure in the capillary
(drops from 30 to 10 mm Hg), 2) hydrostatic pressure in the interstitium (essential zero, therefore you can ignore it),
3) oncotic pressure in the capillary (normally about 28 mm Hg), and 4) oncotic pressure in the interstitium (about 8
mm Hg). Fluid is pushed out of the capillaries on the arterial side of the capillary beds but is almost completely
reabsorbed on the venous side, and any leftover fluid drains by the lymphatics. Two possible cause of edema: if
arterial pressure is high, excess fluid will be pushed out at the arterial end of the capillary bed but won’t be
reabsorbed at the venous end because the oncotic pressure will be insufficient to compensate; alternatively, if
oncotic pressure in the blood is abnormally low (like in certain liver diseases), the fluid will not be reabsorbed on
the venous end. A third cause of edema, which isn’t really discussed in this section, is blockage of the lymphatics—
think the Elephant Man. A fourth cause is venous insufficiency—faulty valves in the leg veins can allow blood to
pool in the lower extremity as a result of increased hydrostatic pressure due to gravity, causing edema and varicose
veins.
What tests might Aunt Gilda want to undergo to investigate her vascular problems further?
A test that she’s likely to have is Doppler ultrasound imaging of her carotid arteries. This test measures blood flow
velocity and can detect turbulent blood flow, as might occur if she has a narrowing or plaque in her carotid artery.
She could also undergo angiography of her carotid and cerebral circulation to look for stenosis of these vessels.
Other cardiovascular tests that can assess hemodynamic functions (though not necessarily in the brain) are Fick
and cardiac thermodilution tests to determine cardiac output, plethysmography to measure volume changes in
different parts of the body, and nuclear imaging to determine if the myocardium is receiving sufficient blood flow.
6.
Prolonged clotting time can be due to several genetic deficiencies in components that contribute to
hemostasis. Please list three common clotting deficiencies and how they impair the normal hemostatic
mechanisms.
It would be helpful to draw out the coagulation cascade and indicate which steps are affected by each deficiency.
Hemorrhagic diseases can be caused by deficiencies in most of the clotting factors or other procoagulant factors.
- Factor VIII deficiency (hemophilia A)- factor VIII functions as a reaction accelerating cofactor in the
activation of factor X, the beginning of the common pathway for the two arms of the coagulation cascade.
- vWF deficiency (von Willebrand disease)- low vWF compromises formation of the platelet plug and the
localization of factor VIII to the site of injury. vWF binds exposed collagen on a damaged vessel and to the GPIb/IX
receptor on activated platelets allowing plug formation to begin. It also carries factor VIII to sites of vascular
injury.
- Prothrombin deficiency- prothrombin is the inactive form of thrombin. Thrombin a central component of
coagulation because it is necessary for cleavage of fibrinogen to fibrin, for activation of factor XIII as well as for
amplification of the coagulation pathway by activating factors V, VIII and XI.
Other relevant deficiencies:
- Factor IX deficiency (hemophilia B, Christmas disease)
- Factor XII (Hageman Factor) deficiency- loss of intrinsic path initiation
- Tissue factor deficiency- loss of extrinsic path initiation
-Vitamin K deficiency- although not genetic, has a significant effect on hemostasis because the function of
factors II (prothrombin), VII, IX and X and proteins C and S all depend on gamma-carboxyglutamic acid
addition by a vitamin K-dependent carboxylase.
7. Describe the major steps by which a complex atherosclerotic lesion forms.
-Subendothelial lipoprotein retention  cytokine release recruits monocytes  monocytes differentiate into
macrophages  macrophages accumulate cholesterol fatty acid esters (CE) [foam cells]  smooth muscle cells
migrate from media to intima, secrete collagen and accumulate lipid  fibrous cap forms  accumulation of
extracellular lipid (from retention and dying foam cells)  necrotic core forms
8.In general, stimuli that increase the heart rate also increase the blood pressure, and those that decrease
heart rate lower the blood pressure. Name two exceptions to this rule, in which the responses of the blood
pressure and heart rate are discordant.
a. Cushing reflex (response to increased intracranial pressure leads to rise in BP via chemoreceptor
stimulation of vasomotor center, but reflex bradycardia via arterial baroreceptors)
b. Atrial stretch baroreceptors (increased firing when venous return is increased, leading to vasodilation, but
heart rate is increased)
9.In sympathectomized patients, what response in heart rate is seen when patients are asked to perform a
Valsalva maneuver? Why is this the case?
Heart rate changes still occur, since the baroreceptors and the vagi are still intact; namely, bradycardia due to
increased intrathoracic pressure which increases BP during the maneuver.