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.
Carboxyhaemoglobin concentration is measured using spectrophotometry, comparing the total absorption spectrum curve to the characteristic curve generated by pure COHb. The concentration is expressed by the ABG machine as a percentage (FCOHb) - a ratio of cCOHb to ctHb.
The principles underlying the detection of methaemoglobin are discussed elsewhere, as are the properties of methaemoglobin. This chapter focuses on the reasons as to why one might have ended up with oxidized haem iron, and how to get out of such a situation. As with all such "why is there too much of substance x" questions, the answer is usually either excessive synthesis, or ineffective clearance. Both mechanisms need to be explored. In the interest of rapidly offering a brief summary to those intolerant of tangential gibberish, a table is available as a list of the major culprits.
This chapter focuses on the properties of methaemoglobin, and the situations where it might be undesirable to have too much haem iron in its oxidised Fe3+ state - i.e. essentially any situation where you are not suffering from cyanide toxicity. Methaemoglobin happens to have a very high affinity for oxygen; additionally it increases the oxygen affinity of non-oxidised haem monomers, thereby producing an impressive left-shift of the dissociation curve. The result is a significant impairment of oxygen-carrying capacity.
The general principles of using absorption spectrophotometry to identify and measure the concentrations of haemoglobin species are discussed elsewhere. This chapter focuses on the use of these principles to measure the concentration of methaemoglobin, expressed by the ABG machine as FMetHb. Methaemoglobin absorbs strongly in the 600-650 nm range of wavelengths, allowing the blood gas analyser to estimate its concentration using the Lambert-Beer law.
The ABG machine reports this variable as Hctc - the little "c" representing the fact that this variable has not been measured directly, but was calculated using an equation, and certain assumptions. The gold standard of haematocrit measurement is of course the old-school centrifuge.
The ABG machine reports this variable as ctHb, the concentration of total haemoglobin. This variable is measured directly, using visible absorption spectroscopy. Total haemoglobin is the sum of all haemoglobin species, including oxygenated and deoxygenated adult haemoglobin, carboxyhaemoglobin and methaemoglobin. This is a measure of potential oxygen-carrying capacity; it does not define the effective oxygen carrying capacity, because it incorporates haemoglobin species unsuitable for oxygen transport.
In the blood gas analyser, the haemoglobin concentration is measured directly, using visible absorption spectroscopy. The local unit features a 128-wavelength spectrophotometer with a measuring range of 478-672 nm. Absorption spectroscopy is based on Lambert-Beer's law, which relates the properties of transmitted light to the properties of the substance through which it is transmitted. The absorbance, in this scenario, is defined as the logarithm of the ratio of the light intensity before and after transmission through the compound. Each haemoglobin species has a different extinction coefficient (ε) and these are known from empiric measurements.
The Severinghaus electrode is essentially a slightly modified glass electrode. The CO2 dissolved in the sample diffuses into the middle compartment of the electrode via a thin membrane. Once inside, the CO2 finds itself in an aqueous solution. For convenience, there may or may not be a bicarbonate solution added to this chamber. The reaction which takes place is an old familiar carbonic acid dissociation equilibrium. Thus, the pH of the solution in the middle chamber changes. The change in pH is completely dependent on the pCO2, provided the temperature and pressure remain constant. This results in a change in potential difference in the glass electrode; and the function of this item has already been discussed at some length in another chapter. Thus, from the change in pH, one can calculate the pCO2.
Leland C. Clark never called his device "the Clark Oxygen Electrode", as such a gesture would probably have been viewed by his contemporaries as mildly disgusting. The paper he published discusses the "continuous recording of blood oxygen tensions by polarography"- it was a "polarographic" electrode, and this is also how it is referred to in some of the earlier literature. The polarogram is the graphed relationship of current and voltage which is discussed at length elsewhere.
The oxygen cathode is essentially an electrolytic cell. The potential difference across the oxygen-containing electolyte allows a reduction of the dissolved oxygen; the oxygen borrows electrons from the cathode and hydrogen ions from the water molecules of the aqueous solution. A satisfactory amount of detail about these methods is available in William L. Nastuk's 1962 textbook, "Electrophysiological Methods:Physical Techniques in Biological Research".
The modern concept of pH requires a primary method measurement in order to maintain validity as a definition. Specifically, some sort of method is required to calibrate standard buffer solutions, against which the pH of all substances can be measured. The experimental apparatus used by IUPAC to assign standard pH values to primary standard pH buffer solutions is based on the Harned cell.
The modern concept of pH can be defined as a number expressing the acidity or alkalinity of a solution as the logarithm of the reciprocal of hydrogen ion concentration or hydrogen ion activity. This is not the definition. One might search far and wide for a simple lay definition, and one would meet no interesting or informative obstacles for many miles. To uncover a proper definition one must descend into the atmosphere-of-Venus-like environment of Pure and Applied Chemistry. There, one may finally discover the 2002 IUPAC definition, as well as the IUPAC-specified international standard for the procedures of pH measurement.
The original concept of pH was developed by Søren Peder Lauritz Sørensen, and involved the concentration rather than the activity of hydrogen ions. This was the result of earlier work by Svante Arrhenius whose 1884 definition of an acid was "something that dissociates in solution to produce hydrogen ions". In order to precisely measure the hydrogen ion concentration without resorting to colour-change tests, Sørensen devised an experiment in which the concentration gradient of ions could be related to the electric gradient between electrodes in an electrochemical cell.
The IUPAC definition incorporates both the Brønsted and the Lewis models of acids and bases. Thus, an acid is "a molecular entity or chemical species capable of donating a hydron (proton) or capable of forming a covalent bond with an electron pair." The two models are complimentary, and coexist easily in the complex minds of chemists, as they are useful for different situations.