FAQs Cardiovascular, Respiratory and Renal Physiology

Asthma

Question

When as pt has and asthma attack due to it being an obstructive problem , I thought the pt would be hypercapnic .. The PBL had the ABGS that showed hypocapnic. I dont follow the rational. Also, when A beta 2 agonist is given , does it initially cause hypoxemia because the vessels were vasodilated and when the beta agonist was given it caused vasoconstriction and this caused a Ventilation/respiration mismatch? 

Answer

the asthma attack caused a big-time mismatch in V/Q  by lowering V to alveoli downstream from constricted and mucus filled airways.

this caused a drop in arterial PO2

this caused stimulation of carotid PO2 receptor leading to hyperventilation (= decreased PCO2).  this would increase PO2 but not enough to compensate for the regions of the lung with low V/Q.

An arterial PO2 < 60 is defined as respiratory failure.  there are two types of respiratory failure:

type 1 = PO2 < 60 with normal or low PCO2 (patients can hyperventilate in response to hypoxia but still have low PO2)

type 2 = PO2 < 60 with high PCO2 (patients are unable to increase ventilation enough to lower PCO2)

memory tool:  type 2 = CO2

A beta 2 agonist may initially cause a drop in saturation by dilating arterioles more than airways, thus worsening V/Q mismatch.

Potassium
I'm finding a few little discrepancies between the currents discussed in class and those in Physiology by Costanzo, and was wondering what to go by. For example, regarding Phase 3, Costanzo never mentions an I(k1), only an I(k), but we had talked about both in class for this phase. Also for phase 4, Costanzo says for action potentials in the ventricles and atria, there is an outward I(k1) current and inward i(Na) and i(Ca-T), but in class we said it was an outward i(k) and inward i(Ca-T) and i(f). The only time Costanzo mentions i(f) is with the SA node action potential. Are these differences really important?

Answer

In contractile myocytes that exhibit fast-response action potentials and a stable phase 4, membrane permeability to potassium is high, largely due a high open probability of inwardly rectifying K channels (these channels carry the IK1 current).  Consequently, phase 4 membrane potential is close to the K equilibrium potential, and there is only a small outward K current.  Permeability to Na+ and Ca2+ is very low, so the inward currents associated with these ions are small.  Neither T-type channels nor channels that mediate the funny current (if) in pacemaker cells are involved here.

In pacemaker cells (e.g. SA node), there are 3 primary currents that are responsible for the phase 4 pacemaker potential:

a. An inward current (if) carried mainly by Na+.  

b. An inward Ca2+ current (iCa) that becomes activated toward end of phase 4, mediated by both L-type and T-type VGCC.  L-type channels are activated near the end of phase 4 and contribute not only to this pacemaker potential, but also phase 0 (i.e. upstroke of the action potential; see attached review). These L-type channels are also those activated by catecholamines, which increase the inward Ca2+ current, thereby increasing the slope of the pacemaker potential.

c. A decreasing outward K+ current (iK) due to inactivation of Kdr (delayed rectifier K channels).

Although not mentioned in current physiology texts, there is also evidence that the sodium calcium exchanger plays an important role in the pacemaker potential by mediating an inward Na+ current (I think this is also mentioned in the attached review).  Also note that the statement in Costanzo that T-type calcium channels mediate phase 0 of the slow response action potential is a mistake.  T-type channels may be involved in the phase 4 pacemaker potential, but not phase 0, as Dr. Partridge mentioned.  Inward calcium current through L-type channels predominantly mediates the upstroke of the action potential in pacemaker cells.

Regarding phase 3:

In a fast response action potential, the rapid repolarization during phase 3 is caused by inactivation of the L-type Ca2+ channels and a relative increase in K+ permeability [mediated primarily via activation of delayed rectifier K+ channels (iK) and inwardly rectifying channels (iK1) ].

For slow-response action potentials, phase 3 is primarily mediated by increased outward K+ current (iK) due to activation of Kdr.

SVT vs. VT

Regarding the question which begins "This EKG was obtained from a 77 year old woman who was recently admitted to the Coronary Care Unit for an acute inferior myocardial infarction...." the question is accompanied by an EKG which shows a narrow complex tachycardia without discernable p-waves. It appears to have left axis deviation (Up in I, Down in aVF). The V leads are not concordant. The answer is keyed as V-tach, not SVT. If this is VT, what did I miss?

Answer 1
I can see why this is confusing. Looking at the QRS complexes they are not as wide and bizarre looking as we usually see in VT although they are definitely widened a little. The thing that really makes it VT is the AV dissociation with the appearance of p waves independent of the QRS complexes (indicated by the arrows). You cannot have AV dissociation with SVT because the atria (and SA node) are depolarized at the same rate as the ventricle, around 150 times/minute. That means that the SA node would never get a chance to depolarize normally and cause a p-wave. 


Answer 2
In short, SVT is an "above the ventricle" arrhythmia. Typical SVTs include: A-Fib, A-Flutter, AVRT, or AVNRT. VT is a ventricular initiated arrhythmia. This rhythm is often a medical emergency as it may digress to VF and significantly compromise systemic perfusion.


On the ECG one could often distinguish between the two by looking at the width of the QRS complexes. VT will be very broad suggesting ventricular delay, SVT tends to be narrow.


In the example question given the QRS complexes appear to be >100 msec (wide) but this is not clear given no little box detail and no print out of intervals. 

Rho Kinase

I just have a quick question I'm having a hard time answering. Does the RhoA/ROCK pathway stimulate or inhibit the MLCP pathway?

Answer

Activation of the RhoA-ROK pathway mediates increased smooth muscle Ca2+ sensitivity by inhibition of MLCP, and provides a major contribution to receptor-mediated Ca2+-sensitization of smooth muscle. Such inhibition of MLCP results in accumulation of phosphorylated MLC and thus greater contraction for a given [Ca2+]i.  

Myocyte Action Potentials and Ion Conductance

summative 2 had MCQ on this.  Figure was flawed.  Here is an accurate figure

Answer
"I think that the scale on the "Ion Conductivity" axis is incorrect. At the end of phase 4, all conductances shouldn't be the same. (It looks sort of like the figure is showing current rather than conductance.) In a graph of conductance, gK should be high, it falls during phase 0 and gradually rises again during phase 2 and 3. gNa is transient during phase 0 as shown and L-type gCa is at a peak during phase 2. Further confusing is the time scale, which is compressed with respect to that of the action potential. The figure below from makes this point. (This image is fromhttp://www.cvpharmacology.com/antiarrhy/cardiac_action_potentials.htm, which along with it's links, provides a pretty clear description of the cardiac action potential.)