Table of Contents

The countercurrent multiplier mechanism in the renal tubule establishes and maintains a concentration gradient that allows the extraction of water from the tubular fluid. This multiplier mechanism is maintained by the countercurrent exchange of solutes in the vasa recta, a process that prevents the washout of solutes from the inner medulla. The intrarenal recirculation of urea from the collecting duct (into the renal medulla and then back into the ascending limb of the loop of Henle) also helps maintain this concentration gradient.

Afterload is best defined in terms of ventricular wall stress produced by the actors which resist ventricular ejection. These factors include ventricular wall thickness and chamber radius, ventricular transmural pressure, aortic and peripheral arterial compliance, inertia of the blood mass, and arterial resistance (which is in turn determined by arteriolar radius).

The loop of Henle comprises two major areas of physiological importance. The water-permeable thin descending limb concentrates the tubular fluid by reabsorbing water; and then the thin and thick ascending limbs dilute it again by reclaiming much of the solutes so that the end product is tubular fluid with extremely low osmolality (as low as 90 mOsm/kg). This part of the nephron is responsible for maintaining the countercurrent multiplier mechanism, and is the drug target for loop diuretics.

This bread-and-butter ICU topic has appeared in the exams many times. The most thorough exploration was afforded by Questions 2a, 2b, 2c and 2d  from the second paper of 2003.  Question 26 from the first paper of 2006 asks again about specific features of history which would be important, and Question 18 from the first paper of 2012 discusses antibiotic management and prognostic issues. Question 7 from the second paper of 2012 looks indepth at the causes of treatment failure, and the investigations for treatment-refractory pneumonia.

Amiodarone is a cardiac glycoside antiarrhythmic and inotrope which defies Vaughan Williams classification. By inhibiting Na+/K+ ATPase, digoxin increases intracellular sodium, which increases sodium-calcium exchange by the Na+/Ca2+ exchanger (INCX) during Phase 1 of the cardiac action potential. The resulting increase in intracellular calcium promotes inotropy. It also acts as a vagotonic agent, which slows conduction through the AV node, and decreases the duration of the action potential mainly by reducing the duration of Phase 2. The slope of Phase 4 is increased, promoting automaticity, but then automaticity is overall suppressed by the vagotonic effects./p>

Amiodarone is a Class III antiarrhythmic with Class I, Class II and Class IV effects. Given acutely as an infusion, it mainly acts as a beta-blocker and calcium channel blocker, increasing the refractory period of the AV node and therefore counteracting supraventricular tachycardias. Prolonged therapy reveals more of a Class I and Class III effect, which decreases the velocity of action potential propagation and decreases the risk of reentry from ectopic minipacemakers. Amiodarone has uniquely tenacious pharmacokinetics, is extensively tissue bound, and has a half life measured in tens of days. ,/p>

The proximal tubule is the site of absorption for about 70% of glomerular filtrate, including most of the filtered solutes. The absorption of both water and solutes is mainly coupled to the reabsorption of sodium, driven by the gradient which is generated by the constant tireless work of Na/K ATPase at the basolateral membrane surface. Most of the glucose bicarbonate and phosphate are also reabsorbed here.

Amniotic fluid embolism occurs when some amniotic fluid gains access to the maternal circulation, often in massive volumes and with catastrophic consequences. It was discovered for the first time by Ricardo Juvenal Meyer in 1926, who was extremely surprised to find whole chunks of  foetal tissue (skin cell, lanugo hairs, intestinal mucin) in the pulmonary vessels of dead mothers. Clearly that was an abnormal finding, but nobody really put two and tow together until a whole case series of sudden maternal deaths was linked to pulmonary embolism of amniotic fluid by Steiner and Lushbaugh (1941). Death occurs typically due to circulatory collapse, or (if that doesn't get you) respiratory failure and severe hypoxia.

Dead space is the fraction of tidal volume which does not participate in gas exchange. It is composed of apparatus dead space and physiological dead space. Physiological dead space is usually measured by the Enghoff modification of Bohr's method, and consists of anatomical and alveolar dead space. Anatomical dead space is the volume of gas in the conducting airways, and alveolar dead space is the volume of gas which ventilates poorly perfused alveoli. The contribution of shunt can increase the arterial CO₂ and give the appearance of increased dead space.

Hypokalemia is the serum manifestation of a whole-body potassium deficit. That potassium is largely intracellular, and so the serum represents a tiny portion of the total. If one were for whatever reason potassium-depleted, one would make an attempt to conserve daily potassium loss (in which the renal loss plays the greatest role).  There is a certain obligatory daily loss of potassium; people whose potassium intake was restricted still produced a certain minimum output. The minimal urinary potassium concentration seems to be about 2-5mmol/L, which means that in the absence of dietary potassium your intracellular reserves will gradually dwindle away

Effect site concentration is the concentration of drug at the site of its biological activity, eg. bound to the receptors. Effect site concentration is proportional to pharmacological effect, whereas plasma concentration may not be. The rate of effect onset is determined by the rate of distribution of the drug from other compartments (i.e. central compartment) into the effect site. Equilibration between the central and the effect-site compartment follows first-order kinetics, described by the constant k^e0.  t_½k^e0 is a value which describes the time taken to achieve 50% effect-site concentration when the plasma levels are maintained at steady state. 

Question 2 from the second paper of 2001 is a question about the differential diagnosis of wheeze. There can be a myriad answers. UpToDate even has a page about this sort of thing.  Question 2 from the second paper of 2007 is somewhat weirder, and asks specifically for causes of a unilateral wheeze.

Transpulmonary pressure (TPP) is the difference between the alveolar pressure (Palv) and pleural pressure (Ppl), for which oesophageal pressure (Pes) is a reasonable surrogate. It is the net distending pressure on the lung parenchyma, and therefore should be the variable we use to adjust our ventilator settings. Unfortunately, it has several problems. You never know ehere the balloon is and what its really measuring, and when it measures something you never quite know whether that pressure is equal across the entire pleura. Also, it migrates. And there is only one RCT in support of this technique, which did not reach statistical significance with hard outcomes. But, it remains a fascinating physiological toy, and companies have been quick to adopty and market this device. You will see it soon in the well-funded private hospital near you.

Glomerular filtration is influenced by Starling forces acting on the glomerulus (for water) and the size and charge barrier of the glomerular filtration membrane (for solutes). The net ultrafiltration rate of the glomerulus depends on the permeability of the filtration surface to water and to the net filtration pressure, which is a balance of hydrostatic pressures and oncotic pressures between the glomerular capillaries and Bowman's space.