Renal

Question 1

Diffusion

Answer 1

solute transport across a semi-permeable membrane generated by a concentration gradient.

Question 2

Convection

Answer 2

bulk-flow of solute across a semi-permeable membrane together with a solvent in a manner that is dependent on transmembrane pressure and membrane characteristics

Question 3

Dialysis dose

Answer 3

equivalent to the effluent rate in ml/kg/hour.

Effluent rate is the ultrafiltration rate for haemofiltration (CVVH), or the sum of ultrafiltration rate and dialysis rate for CVVHDF

Question 4

Transmembrane pressure

Answer 4

the hydrostatic pressure gradient across the membrane.
It is the driving force that causes ultrafiltration

Transmembrane pressure (TMP) = (Filter pressure + Return pressure) / 2 – (Effluent pressure)

Question 5

sieving coefficient

Answer 5

SC is a measure of how effectively a substance is removed through the filter.

SC = 0 means the substance is not filtered at all e.g. protein sized molecules

SC = 1 means the substance is completely filtered e.g. urea, creatinine

It depends upon the properties of the membrane and on the rate of ultrafiltration

Sieving coefficient (SC) = Ultrafiltrate concentration / Blood concentration

Question 6

determinants of sieving coefficient

Answer 6

Molecule size of the solute
Protein binding of the solute
Charge of the solute and of the filter membrane
Size and number of pores in the filter membrane

Question 7

filtration fraction

Answer 7

the volume of plasma removed from the dialysed blood by ultrafiltration

ideal filtration fraction at a haematocrit of 0.30 is around 0.25

Question 8

filtration fraction formula

Answer 8

Filtration fraction = Ultrafiltration rate / Blood flow rate

more accurately:
Filtration fraction = Ultrafiltration rate / (blood pump rate × 1 – Haematocrit)

Question 9

Advantages of pre-dilution

Answer 9

Ultrafiltration rate is not limited by the blood flow rate (can give more pre-dilution fluid to increase ultrafiltration)

Elution of urea from RBCs is enhanced (urea migrates out of them into the diluted plasma)

Filter life is increased, as the haematocrit throughout the filter remains reasonably low

May avoid the need for circuit anticoagulation

With increased filter lifespan, one may achieve a higher solute clearance over the whole (longer) session, even though hourly solute clearance may be decreased.

Question 10

Disadvantages of pre-dilution

Answer 10

Solute concentrations are decreased, and thus the concentration gradients are decreased in the countercurrent filter: the result is a decreased rate of solute clearance

A larger amount of predilution fluid is required

Question 11

Advantages of post-dilution

Answer 11

Clearance of solute is directly related to ultrafiltration rate.

A higher solute clearance rate is produced

A smaller volume of replacement fluid is required (cost.)

Filter lifespan can remain unaffected if protected by adequate anticoagulation

Question 12

Disadvantages of post-dilution

Answer 12

The rate of ultrafiltration is limited by the blood flow rate: you cannot order too much fluid removal, because otherwise the end-filter haematocrit will be too high. (This is why a smaller volume of replacement fluid is required!)

Because ultrafiltration rate is limited by filtration fraction (anything beyond 25% is too much), one may not achieve the desired “optimal” dose of 25ml/kg/hr with the normal blood flow rates of CRRT.

Filter life may be degraded by high end-filter haematocrit

Question 13

indications for dialysis

Answer 13

Oliguria (less than 200ml in 12 hours)
Anuria (0-50ml in 12 hours)
Urea over 35 mmol/L
Creatinine over 400mmol/L
Potassium over 6.5mmol/L
Refractory pulmonary oedema
Metabolic acidosis with pH less than 7.10
Hypernatremia over 160mmol/L
Hyponatremia under 110 mmol/L
Temperature over 40°C
Complications of uraemia: encephalopathy, pericarditis, myopathy or neuropathy
Overdose with a dialysable toxin

Question 14

When to start dialysis in chronic renal failure

Answer 14

Start when the GFR has fallen to below 15ml/min
Definitely start before the GFR falls to below 6ml/min
Symptomatic uremia
Inability to control fluid balance
Inability to control blood pressure
Progressive deterioration in nutritional status
Diabetics may benefit from an earlier start

Question 15

Complications of RRT

Answer 15

Access complications
Haemolytic complications
Inflammatory response
Blood loss due to circuit loss
Hypothermia
Electrolyte disturbance
Hypocapnia
Hypoxia - due to increase in the activity of nitric oxide synthase, which countracts the normal mechanisms of hypoxic pulmonary vasoconstriction.

Malnutrition due to dialytic nutrient loss
Delayed renal recovery
Complications related to anticoagulation

Question 16

Proposed causes of delayed renal recovery in RRT patients

Answer 16

Haemodynamic instability
Haemofilter membrane-induced complement and cytokine activation, with subsequent “cytotoxic” tubular injury (analogous to septic nephropathy).
Trophic hormone depletion (missing paracrine triggers for nephron regeneration)

Question 17

Dialysis disequilibrium syndrome

Answer 17

Occurs with IHD
- the movement of small solutes so rapid and in such massive volume, that the concentration of chronically accumulated uraemic wastes in the brain becomes substantially greater than the extracellular fluid.

The resulting osmotic movement of water can give rise to cerebral oedema, which manifests at first as confusion, progressing into unconsciosness.

Question 18

General Principles of Antibiotic Dose Adjustment in CRRT

Answer 18

Antibiotics with time-dependent killing:
if the drug is rapidly cleared by CRRT, the dosing interval should be decreased (i.e. the doses need to be given more frequently)

Antibiotics with concentration-dependent killing:
if the drug is rapidly cleared by CRRT, the actual dose should be increased, and dosing interval should remain more or less the same.

If the RRT is intermittent (eg. SLED):
the antibiotics should be given after the end of each session.

Question 19

Factors which Influence the Clearance of Drugs by CRRT

Answer 19

Molecular weight

Volume of distribution - Drugs with a small volume of distribution will be easily cleared.

Protein binding - Only the unbound “free” fraction will be cleared by any RRT technique.

Membrane adsorption - Some drugs will be cleared by adsorption to the dialyser membrane. eg colistin

Molecular charge

Question 20

Methods of Prolonging the CVVHDF Filter Lifespan

Answer 20

Nothing whatsoever (+/- regular saline flushes)

High flow rate

Pre-dilution

Unfractionated heparin

Reversal of anticoagulation at the end of the circuit

Low molecular weight heparin

Warfarin

Platelet function inhibitors:NSAIDs, aspirin, etc

Citrate

Direct thrombin inhibitors: Hirudin / Lepirudin/ Bivalirudin / Argatroban

Heparinoids (Danaparoid)

Xa inhibitors: Fondaparinux

Serine protease inhibitors: Nafamostat - Very short half-life (8 min)
- Suppresses neutrophil activity and may cause agranulocytosis

Prostacyclin (PGI2)

Question 21

HOw does citrate work

Answer 21

Calcium chelator

Factors 2, 7 9 and 10 are clotting cascade proteins which require calcium to function

The net effect is the inhibition of thrombin formation.

In order to work, the citrate dose must be adjusted to achieve an ionised calcium concentration less than 0.4mmol/L within the filter.

Metabolic fate of citrate

Question 22

The cardinal features of citrate toxicity are:

Answer 22

High anion gap metabolic acidosis OR metabolic alkalosis

Low ionised calcium with a high (or normal) total calcium

Question 23

The predisposing factors include:

Answer 23

Liver disease (unable to metabolise the lactate)
Coagulopathy (requirement for regional anticoagulation of the CRRT circuit)
HITTS (or any other contraindication to the use of heparin)
Hypocalcemia
Decreased hepatic blood flow (eg. in sepsis or other shock states)