Table of Contents

Affinity in chemistry is the tendency of dissimilar chemical species to form chemical compounds. Dissociation constant (K_d ) is the rate constant of dissociation at equilibrium, defined as the ratio k_off / k_on (where k_off  and  k_on  are the rate constants of association of the drug off and on to the receptor). When K_a is high, K_d is low, and the drug has a high affinity for the receptor (fewer molecules are required to bind 50% of the receptors).  The major factors which affect affinity and dissociation constant in clinical pharmacology are temperature and the presence of a catalyst

Myoglobin is a small monomeric haem protein found in skeletal muscle and myocardium. It contains one oxygen binding site (for one O₂ molecule). The oxygen-myoglobin dissociation curve is hyperbolic rather than sigmoid. Myoglobin has a very high affinity for oxygen: the p50 is ~ 2.7 mmHg. Its role is to maintain the oxygen supply to exercising muscle. The total oxygen store of myoglobin in the human body is around 200-300ml, equivalent to about 7-10 seconds of muscle activity/p>

Diffusion and perfusion are the two main processes which govern the rate of alveolar-capillary gas transfer. Diffusion-limited gas exchange is where the rate of gas uptake in the capillary is determined by the rate of diffusion across the blood-gas barrier (eg. where the rate of diffusion from alveolus to blood is very slow). Perfusion-limited gas exchange is where the rate of gas uptake in the capillary is determined by capillary blood flow, eg. where the rate of gas diffusion into the capillary is very rapid. Carbon monoxide is a diffusion-limited gas, whereas oxygen is perfusion-limited under most normal circumstances.

Diffusion of respiratory gases is governed by Fick's Law and Graham's Law. As such, the main determinants of diffusion are the density of the gas, its molecular size, temperature, solubility and fluid viscosity, the partial pressure gradient between compartments, the surface area of the membrane and the speed at which the solvent is moving past it. The characteristic feature of this topic seems to be the large number of numerical values which, upon closer examination, are not particularly well supported by references, or which originate in ancient papers from the 1940s. Most textbooks are quite happy to plagiarise from one another and by some intergenerational cut-and-pasting, these values have been transmitted unchanged to the modern day. The CICM trainees are advised to regurgitate these numbers without questioning their origin. 

"The diffusing capacity is defined as the volume of gas that will diffuse through the membrane each minute for a partial pressure difference of 1mmHg. For oxygen, the equation is ( D_LO2 = O₂ uptake / PO₂ gradient). The normal value for oxygen is about 20-30 ml/min/mmHg. It is usually measured with the use of carbon monoxide (as D_LCO, as this is is non-invasive and does not require arterial puncture.

The "carbon dioxide cascade" is not a term which has ever been used to describe a stepwise decrease in the partial pressure of carbon dioxide between the mitochondria and the atmospheric air. Precise measurements at most of the steps are impossible. Depending on tissue metabolism, the starting partial pressure may be as high as 100 mmHg (maximally exercising muscles) or 20 mmHg (metabolically inactive bone and fat). The only firm measurement which appears consistently across textbooks is the mixed venous PCO₂, which is usually said to be 46 mmHg.

The pulmonary circulation is a low pressure, highly elastic system, with vessel walls which are much thinner and less muscular than the systemic circuit. The pulmonary trunk divides into pulmonary arteries which can be divided into elastic (large), muscular (small) and nonmuscular (the smallest), though further subdivisions are histologically apparent. Pulmonary arteries and veins travel with bronchi, nerves and lymphatics in bronchovascular bundles, which are extensions of the visceral pleura. Pulmonary veins are thinner and more collagen-rich than pulmonary arteries. The bronchi are supplied by the systemic circulation which arises from the intercostal arteries on the right and from the aorta on the left.

Alveoli are the basic unit of the gas exchange surface. Their adaptation to their main function (to exchange gas) is to be extremely thin, with a vast surface area, and relatively high resistance to mechanical stress They have a largely polyhedral shape, with extremely thin walls, which are all connected to each other giving the macrostructure elasticity and strength. The alveoli are composed of Type 1 and 2 pneumocytes, as well as capillary endothelial cells, fibroblasts, macrophages and mast cells.

The principles governing the behaviour of gases in solution are fundamental to the understanding of gas exchange and gas transport in the blood. The major topics of this chapter are Dalton's and Henry's Laws, and the influence of temperature on the solubility of gases in body fluids.

This chapter is a summary of the pharmacological properties of vasopressin, with a focus on its use as a vasoactive infusion. Of course, when one normally calls something a "summary", one implies that the information is sensibly condensed into several small easily digestible snack-like pieces. This definition cannot apply to the following, which more closely resembles a multiple-course degustation banquet, a structured feast the excesses of which end in a messy pile of bloated drunks. Some of the information is repeated from previous discussions of the physiology of vasopressin as it relates to the control of extracellular osmolality; the rest is material more relevant to people who deploy vasopressin in the treatment of shock.

This chapter focuses on the ways in which a changing CO2 concentration might alter the pH of a solution, particularly that of your precious bodily fluids. The physiological consequences of acidaemia and alkalaemia are discussed in dedicated chapters, as are the various effects of having an excessively high or precipitously low blood CO2 level (independent of pH changes). A chapter which summarises the bedside rules and equations used in the interpretation of blood gases is also available as a brief overview of the empirically derived formulae which describe acute and chronic compensation for acidosis and alkalosis.

Human bodily oxygen stores consist of oxygen incorporated into body molecules (the human body is approximately 61-64% oxygen by weight) and a reservoir of oxygen which is available for metabolism. That reservoir consists of dissolved oxygen as molecules of O₂ in blood and generally in body water, bound gas complexed with other molecules (eg. haemoglobin), and as free gas in the lung volumes, of which the FRC is the most clinically important.

In spite of being a vitally important metabolite and an essential ingredient of normal multicellular life, oxygen is nonetheless not excused from being treated as a drug, with side effects and contraindications. Given that virtually all patients in the ICU end up receiving oxygen, it seems reasonable to expect the competent ICU trainee to be intimately familiar with its properties - as it would be madness to funnel litres of something into one's patients while knowing nothing about its effects.

The CO₂ dissociation curve describes the change in the total CO₂ content of blood which occurs with changing partial pressure of CO₂. This curve is more linear and steep than the oxygen-haemoglobin dissociation curve. It has no plateau, and as the result of this, shunt has little effect on CO2 (increasing the ventilation of already well-ventilated regions will improve CO2 exchange, even though it will not improve oxygenation).