A free online resource for Intensive Care Medicine.
An unofficial Fellowship Exam (CICM Part 2) preparation resource.
Deranged Physiologyis a slowly growing archive of discussions and study notes relevant (or if not relevant, then at least interesting) to the practice of intensive care medicine. The content provides an introduction to the fundamental themes in intensive care: mechanical ventilation, vasopressors, electrolyte management, hemodynamic monitoring, dialysis, and so forth. Attention is directed at equipment in intensive care, and there are attempts to revisit interesting pharmacology and physiology. The aim of this resource is to supplement the bedside teaching of senior staff, and to consolidate resources for intensive care trainees in the initial stages of their training.
Since Arrhenius started being taught in schools, and since most people started going to school, the concentration of hydrogen ions became a household term, synonymous with pH. Even as Sørensen revised his definition in terms of activity rather than concentration, people were taking up the notion that in every glass of water, some 107 protons and hydroxyl ions were lurking, free and naked, ready to tear molecules to shreds. Plainly, this is insane.
Standard base excess is the concentration of titrable base when the blood is titrated back to a normal plasma pH of 7.40, at a normal pCO2 ( 40 mmHg) and 37° C, at the actual oxygen saturation, AND at an "anaemic" haemoglobin concentration, to account for the buffering of extravascular fluid by haemoglobin. It is reported as cBase(Ecf), to reflect the fact that the entirety of the extracellular fluid is under investigation here. In summary, it is the actual base excess adjusted to a Hb level of around 50g/L.
Actual base excess is the concentration of titrable base when the blood is titrated back to a normal plasma pH of 7.40, at a normal pCO2 ( 40 mmHg) and 37° C, at the actual oxygen saturation. It is reported as cBase(B)c. This base excess represents the metabolic contribution to the change in base excess. In essence, this is what the base excess should be if all the non-metabolic influences were corrected.
Standard bicarbonate is the concentration of bicarbonate in the plasma from blood which is equilibrated with a normal PaCO2 (40 mmHg) and a normal pO2 (over 100 mmHg) at a normal temperature (37°C). Usually, it is obtained by solving the Henderson-Hasselbalch equation to get a bicarbonate value when the pH is known and PaCO2 is 40mmHg. This bicarbonate level represents the metabolic contribution to the change in bicarbonate. It was introduced in 1957 by Jorgensen and Astrup. In essence, this is what the bicarbonate should be if all the non-metabolic influences were corrected. It answer the question, "how much would my patient's bicarbonate be if I were ventilating them properly?".
Actual bicarbonate is the concentration of hydrogen carbonate in the plasma. The ABG machine usually reports this as cHCO3-(P). It is a derived variable. One is interested in the bicarbonate value because it is the most important extracellular fluid buffer, accounting for 75% of total buffering in metabolic acid-base disturbances (the rest being performed by blood proteins, such as haemoglobin).
There is a vast selection of chloride-sensisive ionophores available. Traditionally, quaternary ammonium salts have been used as a chloride-selective ionophore admixture into PVC, together wih a plastiiser like o-nitrophenyl octyl ether (NPOE). However, researchers and clinicians comlained that these membranes showed poor selectivity over salicylate anions and heparin (both with a high anionic charge). Subsequently, ionopores such as mercury(n) EDTA and indium porphyrins were developed. Less rare-earth-dependent solutions today include such unpronounceable neutral carriers as tridodecylmethylammonium chloride (TDMAC).
The majority of bound calcium travels around in the circulation in a complex with albumin. It binds reversibly to twelve of the sixteen exposed imidazoline binding sites on the albumin molecule. Of these available cation-binding sites, only 10-15% are occupied (i.e. only one or two sites). This means there are plenty of available sites to bind other cations (eg. magnesium) and the divalent cation species rarely enter into binding site competition with one another, particularly as there are so few of them (1-2mmol/L). On the other hand, the hydrogen (or hydronium) cation is a constant source of competition. The positively charged water molecule species work to displace calcium from its binding sites.
The generation of a potential difference across the electrode membrane rests on the traffic of free calcium ions. Obviously, if abovementioned ions are tied up in some sort of chelation complexes or are busy encrusting albumin, they will not be measured by the analyser. Nor will they perform any useful work. Hence, this electrode measures the only biologically relevant calcium concentration, which is the ionised calcium.
Unfortunately, Radiometer aren't very specific in their description of their electrode. Given the high degree of selectivity of the electrode, and the absence of a solvent reservoir, one might surmise that this is not one of those "saturated wick" liquid membrane electrodes, where the selectivity is conferred by a hydrophobic oil-based solvent impreganted with ionophores, soaked into a porous ceramic frit. Rather, it may be a ceramic loosely based on one of the old-school glass sodium electrodes, a staple of the electrochemistry lab since the 1950s.
The potassium-selective electrode features a PVC membrane doped with a potassium-selective ionophore. Radiometer do not specify which, but valinomycin is historically a popular choice. It is a macrolide antibiotic with a ring-shaped molecule. The potassium ion measures about 1.33 angrom across, and just about fits the cavity inside that ring, which is between 2.7 and 3.3 angstrom across. An electrode with a valinomycin-impregnated PVC membrane can be up to 5000 times more selective for potassium when compared to sodium.
The ion sensitive electrodes in the ABG machine measure the concentrations of potassium, sodium, calcium, chloride and lactatem as well as non-ionised glucose. Similar principles of operation apply to each electrode, and they are coupled into a "electrode chain" in the blood gas analyser. For a detailed reference on this topic, I refer the readers to Nallanna Lakshminarayanaiah's Membrane Electrodes (2012)- it is a thorough treatment of this subject. Martin Frant has also published twoexcellent articles detailing the ascent of the ion selective electrode as a tool of point-of-care measurement.
This is an idealised value calculated from the measured PaO2 at a standard set of conditions (pH 7.40, pCO2 40mmHg, and in the absence of dyshaemoglobins), represented as p50(st). By "normalising" the potentially very abnormal environment of the critically ill patient's bloodstream, the p50(st) value eliminates the effect of everything except 2,3-DPG.
This is the partial pressure of oxygen required to achieve 50% haemoglobin saturation. In the ABG machine, this value is extrapolated from the measured PaO2 and sO2. It is represented as p50, in contrast to the p50(st) which is an idealised value calculated from the measured PaO2 at a standard set of conditions (pH 7.40, pCO2 40mmHg, and assuming the absence of dyshaemoglobins). The oxygen-hemoglobin dissociation curve represents the affinity of hemoglobin for oxygen. The p50 value represents a mid-point in this curve, and gives us information regarding that affinity.