Respecto al Derecho Comparado

Simplistically, the two predominant techniques employed in terms of renal support for patients with acute kidney injury may be viewed as either diffusion based (dialysis) or convective (filtration) in nature. Hybrids of these techniques are also available and may offer theoretical advantages, but in order to understand any potential benefits of one technique over another, the fundamental processes involved must be understood. Both convection and diffusion are intimately related in that both processes are required for the separation of molecular species and although haemodialysis, for example, is viewed as a diffusive therapy, it also relies on convection. Similarly, techniques such as haemofiltration relies, in part, on diffusion as well as convection [1].

Convection describes the movement of any given molecular species within the medium in which it is embedded. The movement of any given molecule is at a speed identical to that of the components of the medium itself and thus all molecular components consequently move at the same rate (Fig. 14.1a). It follows, therefore, that convection per se is of little use in terms of separation of molecular species.

However, convection is an essential process in that it allows transport of molecular species to a boundary where they can be separated: this may be via a semipermeable

M. Joannidis

Medical Intensive Care Unit, Department of General Internal Medicine, Medical University, Innsbruck, Austria

L.G. Forni (*)

Department of Intensive Care Medicine, Royal Surrey County Hospital NHS Foundation Trust, Surrey Perioperative Anaesthesia Critical Care Collaborative Research Group (SPACeR) and Faculty of Health Care Sciences,

University of Surrey, Guildford, UK e-mail: [email protected]

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membrane, for example. Therefore, without convection, diffusive therapies could not occur efficiently. Convection is often thought of as the process which drives ultrafiltration, the removal of water from a solution. However, water removal in dialysis is actually accomplished through forced diffusion through pressure across a semi-permeable membrane. Where highly permeable membranes are used such as in haemofiltration, the predominant driving force is hydrostatic promoting convec-tion through the filter. Given that convecconvec-tion implies that all molecular components move at the same rate then all molecular components will travel with the water (so-called solvent drag) but molecular separation will also depend on the characteristics of the membrane or filter employed (Fig. 14.1b) [2].

Diffusive therapies rely on several phenomena including ordinary diffusion and forced diffusion. Ordinary (or Fickian) diffusion describes the molecular movement induced by random movements coupled to the non-uniform distribution in space of the species. This is shown in Fig. 14.1b, where eventual uniform distribution of molecular species will be seen within a solution. The rate of this process is defined by the diffusive flux. The flux is defined as the number of molecules that pass through a unit area in a unit time. Clearly the flux is also dependent on any concen-tration gradient involving the diffusing substance and this process, for any given molecular species A, is described by Fick’s law [3]:

N_A = − ∇ D C_{A A}

where Ñ_C is the gradient and D is the Fickian diffusivity. Ordinary diffusion effec-tively scatters molecular species throughout the medium and is dependent on numerous factors including molecular size and properties of the solution.

Separation, however, is determined by the introduction of a further element such as a membrane or gel. These will affect diffusion coefficients significantly, allowing molecular separation to occur, which in turn is limited by the available concentra-tion gradients. Forced diffusion describes the applicaconcentra-tion of an external force which acts differently on the molecular species present facilitating separation. Thus in a

a b

Fig. 14.1 (a) Representation of unhindered ordinary diffusion demonstrating a non-uniform dis-tribution and movement throughout the solvent. (b) Representation of convection without diffu-sion moves all molecular species equally and does not result in separation

dialysis machine separation is enhanced not only by the membrane but by concen-tration gradients (ordinary diffusion) but also by pressure changes through the application of blood pumps (forced diffusion). In practice this results in the pas-sage of a molecular species along a concentration gradient, and this solute transport can be expressed as:

Jd DTA= ∂

∂









c x

where DTA are the diffusion coefficient (which varies with the cubed root of the molecular weight), temperature and the surface area of the membrane and ∂c is the concentration gradient across the membrane with ∂d being the membrane thickness.

This differs from convective based treatments (Fig. 14.2) where clearance of a molecular species is, as indicated, driven by hydrostatic pressures and convection.

The hydrostatic pressure driving convection is that pressure generated across the membrane (TMP). This transmembrane pressure is defined as:

TMP Pb Pd= − − π

where Pb is the hydrostatic pressure in the blood compartment and Pd is the hydro-static pressure on the ultrafiltrate side of the membrane. The oncotic pressure is given by π. It follows from this equation that convective flux (Jf) of any given molecular species will be given by:

Jf = Kf × TMP

with Kf being the membrane permeability coefficient. The rate at which molecular species cross the membrane depends on the membrane rejection coefficient (σ) which is effectively zero for small species such as urea but approaches 1 for larger molecules such as albumin. The sieving coefficient (Sc) is given by:

Sc= −1 σ

This can be determined by measuring the concentration of a given solute in the plasma water and the ultrafiltrate. Thus a simple view of solute clearance (K) in convective treatments is the product of:

K= Qf. Sc

where Qf is the ultrafiltration rate. It follows that where Sc = 1, the clearance is equal to Qf. Solute clearance using diffusion-based systems may be calculated from:

K=

(

)

with Qdo and Cdo being the dialysate effluent flow and solute concentration in the effluent dialysate (that leaving the dialyser). Cbi is the concentration of the solute of interest entering the dialyser [4]. In summary, diffusion provides the main basis for the separation of molecular species in dialysis aided by convection, whereas in fil-tration convection is aided by diffusion, and as such the two processes often act simultaneously with any division being somewhat artificial.

Typical SettingsInermittent Haemodialysis (IHD) TMP 0

TMP 0 dialysate

dialysate + fluid removal (effluent)filtrate (effluent) substitution fluid dialysatefiltrate + dialysate (effluent)

dialysate

P PP

P

TMP 0 P P

P

substitution fluidTMP 0 PP PPPP

Continuous Haemodialysis (CVVHD)Continuous Venovenous Haemodialfiltration (CVVHDF)Continuous Venovenous Haemofiltration (CVHD)

Type of Renal Replacement Therapy Blood Flow (QB) Dialystae Flow (QD) Filtrate Rate (QF) Convection Diffusion Adsorption Schematics show an outline of the techniques described. P = Pump and TMP = Trans Membrane Pressure. Typical settings are outlined as are the predominant physiochemical processes involved.

+ +++ +

+ +++ +++++++ +–+++ +

200–400 ml/min 500–800 ml/min10–35 ml/min80–150 ml/min150–250 ml/min100–250 ml/min 10–35 ml/min 10–50 ml/min25–50 ml/min Fig. 14.2Schematics show an outline of the techniques described. P Pump and TMP Transmembrane Pressure. Typical settings are outlined, as are the pre- dominant physiochemical processes involved