Principles of dialysis Flashcards
What’s the average length of treatment for IHD and CRRT?
IHD usually is 4-5h
CRRT is >24h
List 3 renal replacement modalities?
Extracorporeal: CRRT and IHD
Intracorporeal: Peritoneal dialysis
The type of RRT is determined by…
The prescription and treatment type NOT by the type of machine selected
Which of the RRT modality provides the most flexibility in terms of type of treatment that can potentially provide?
IHD
Regarding the dialysis catheter there is an ‘arterial’ and a ‘venous’ line - what do they mean?
It has nothing to do with the type of blood processed as in dialysis (vs ECMO) it is always venous blood. It just indicates the direction ‘to’ (arterial) and ‘from’ the dialyser (venous).
The hemodialysis apparatus is divided into _____ circuit and a _____ circuit. Both meet at the _____
blood
dialysate
dialyser
What’s the main difference in terms of dialysate management between IHD and CRRT?
In IHD the dialysate is generated from purified water + acid concentrate + bicarbonate
In CRRT the dialysate is provided in sterile bags
Briefly describe the process of water purification in IHD
From tap water the water purifier passes it through particulate filters, carbon sorbents for organic solutes, water softeners, deionization beds and ultimately performs reverse osmosis
What is reverse osmosis?
It is the most important process of water purification in IHD machines. The process uses high pressure to push water through a semi-permeable membrane.
This membrane has tiny pores that only allow water molecules to pass through. Larger particles, like salts, bacteria, and other contaminants, are too big to go through and are left behind.
It’s called reverse osmosis because it works in the opposite way of natural osmosis. We apply pressure to push water in the opposite direction, from an area of high solute concentration (more impurities) to low solute concentration (clean water).
Some water purification processes uses an additional method by applying ‘ultraviolet light’ - what is the main risk entailed with this technique?
Ultraviolet light kills bacteria and although the bacteria themselves are too large to pass through the semipermeable membrane during the purification process, LPS released upon bacterial death can pass into the ‘clear water’ and contaminate the final dialysate.
What is an ‘ultrapure dialysate’?
It is a dialysate that undergoeas an additional filtration process within the dialysis machine (NOT the water purifier)
How can we manipulate the final solute concentration of the dialysate?
- type of acid solution
- amount of bicarbonate solution to be added to the dialysate
- Na concentration can be directly programmed, however this will influence the dilution of the acid concentrate (higher sodium = lower dilution)
Which type of solute exchange mechanism is used by the native kidney?
Convection: hydrostatic pressure + solute drag
Diffusion is a consequence of _____
random molecular movements (molecular kinetics) that follow the law of probability.
The velocity of a molecule in solution is inversely proportional to the molecular weight (smaller molecules are faster and have more chances to encounter a pore in the membrane)
Diffusion is mainly determined by ____
- molecular size
- concentration gradient
What is Ko?
Ko is the mass transfer coefficient derived from the ratio of D/X (diffusivity over membrane thickness)
It is an essential part of Fick’s law in the diffusion process
What is KoA?
mass transfer area coefficient
It is a theoretical number that describes the maximum clearance of a solute across the dialyser when the blood flow (Qb) and the dialysate flow (Qd) are infinite
Formula to calculate KoA
KoA = [(Qb x Qd)/(Qb-Qd)] x ln [(1- (Kd/Qb) / 1- (Kd/Qd)]
What is Kd and how can it be calculated?
Kd is the diffusive clearance of the dialyser
Kd = Qb x [(BUNin – BUNout)/BUNin]
Extraction ratio formula (diffusion)
ER = (BUNin – BUNout)/BUNin]
What is the KoA used for?
It is used to compare different dialyser.
KoA is specific for a certain solute AND a certain membrane/dialyser
What is Ro?
It is the resistance (distance/diffusivity) a solute needs to overcome to get from the blood into the dialysate during DIFFUSION.
Ro = Rb + Rm + Rd
Rb = blood resistance
Rm = membrane resistance
Rd = dialysate resistance
What is the most important component of Ro?
The thickness of the dialyser membrane followed by its diffusivity
How can diffusion efficiency be improved?
decreasing the resistance –> decreasing membrane thickness
High efficiency dialysers are characterised by _____
high urea KoA
however to be advantageous a high Qb is also needed as at low Qb the Urea Kd is almost the same for both high and low efficiency dialysers
Small MW = ____ D
Middle MW = _____ D
Large MW = _____ D
<500
500-15000
>15000
URR % formula
URR % = [(BUNpre - BUNpost)/BUNpre] x 100
Which is more important in the diffusion of particles, MW or membrane pore size?
MW
Most molecules can fit in the majority of membrane pores, however if larged MW = less velocity = less chances to encounter a pore
Difference between clearance and solute removal rate
clearance refers to the volume of plasma that is completely cleared from a solute
solute removal rate is a first order process which is directly proprotional to the solute concentration
Since the solute removal rate depends on the initial solute concentration, with very high initial concentration the drop can be very sharp - how can we make the drop less dangerous?
It can be made safer by starting with a lower Kd (or Qb) and slowly increasing it during treatment
What % of dogs presented for dialysis due to AKI are severely over hydrated?
Up to 50%
Ultrafiltration
Movement of water across a semipermerable membrane. A transmembrane pressure (TMP) has to be generated to initiate ultrafiltration.
What are the main determinants of the ultrafiltration rate?
- TMP
- hydrostatic permeability
- surface area of the membrane
Fick’s law - ultrafiltration
J = TMP / u x Rt
u = viscosity
Rt = total resistance
What is Kuf?
Amount of fluid (mL) transferred per hour for each 1mmHg of transmembrane pressure
Ultrafiltration rate formula
Ultrafiltration rate = TMP /Kuf
What is the minimum TMP value to overcome plasma oncotic pressure?
25 mmHg
Define ‘backflow’
Fluid shift from dialysate to blood.
It occurs when a negative transmembrane pressure develops.
Some hemodialysis machines will require a minimum amount of TMP and ultrafiltration to prevent backflow
Ways of achieving ultrafiltration
- pressure control - older and less reliable method which regulates ultrafiltration by modifying TMP
- volumetric control - modern method which determines ultrafiltration by an ultrafiltration pump. UF is checked by measuring the volume of dialysate in vs volume dialysate out
High flux vs low flux dialysers
High flux = high Kuf
High flux refers to____
High efficiency refers to ____
ultrafiltration and Kuf
diffusion and KoA
TRUE or FALSE
Rate of fluid removal is usually limited by Kuf
FALSE
In veterinary medicine Kuf rarely limits the rate of fluid removal. It is the patient size that determines the max safe fluid removal rate.
No more than 10ml/kg/h –> monitor parameters via critline to dectect early signs of hypovolemia
According to Kopency et al. which are the main variables associated with ultrafiltration-related complications?
- higher initial blood volume change (within 15-30 min)
- lower initial venous oxygen saturation
- lower nadir venous oxygen saturation
- higher temperature prior to treatment
- higher total extracorporeal circuit volume
- lower post-treatment BUN
- lower pre-treatment PCV
Convection
Removal of solutes by solvent drag
What is the max size of molecule removed via convection?
40K Dalton
TRUE or FALSE:
Convection influences diffusive process
FALSE
No, it doesn’t as solutes moves together with the solvent
Sieving coefficient
S = [x] filtrate/ [x] plasma
Convective clearance (Kx)
Kx = Quf x Sx
Hemodiafiltration
CRRT using both convection and diffusion
According to a human metanalysis (Mostovaya et al. 2014) post-dilution HDF showed _____ compared to HD
reduction of all-cause and cardiovascular mortality and a dose-response relationship between convective volume and outcome
What are the main limiting factors of IHD/CRRT?
- lipid solubility
- protein binding
- volume of distribution
What’s the significance of ‘effective MW’?
I.e. naproxen is a small molecule (MW 230g/mol) however due to the high protein-binding its effective MW includes albumin (68K dalton)
What are the most important characteristics of a HP membrane?
- biocompatibility
- selectivity
What’s the main difference between HD/CRRT and HP?
HD/CRRT remove free (unbound) substances vs HP can remove bound forms
Van der Wall forces _____ adsorbs compounds
reversibly
i.e. if another substance with higher affinity to the compound bounded passes through the membrane this will release the compound once again into the plasma
This is why substances with <90% bind to albumin have extraction ratios of >80% but when the substance has >90% affinity with albumin the extraction ration falls
Why is the HP filter sometimes followed by HD or CRRT?
The HP filter (especially if not a very selective resins) can bind other plasma substances like glucose, lytes, etc.
It is usefull to further process the blood with a dialysate that can correct these deficiencies
What does a Vd>0.6L/Kg indicate?
Lipophilicity, protein or tissue binding
In people a Vd >1-2L/Kg is usually a deterrent otherwise extracorporeal removal
If there is no saturation of the membrane, HP work as a 1st order kinetics
Clearance formula for HP
Clearance = Qb (1-Hct) x [(Ca-Cv)/Ca]
Ca= pre-cartridge concentration
Cv = post-cartridge concentration
One vs two compartments kinetics
Clearance in IHD depends on ____ vs in CCRT depends on ____
Qb
Qd
To achieve 100% clearance in CRRT ____
Qb > 3x Qd
If Qd > 1/3 of Qb it’s a waste of dialysate (which is very costly)
Filtration fraction
Proportion of plasma filtered across the membrane
FF = Quf / Qp
Qp = Qb x (1-HCT)
What’s the target FF?
Not >25%
Clearance for:
- CVVH post-filter replacement
- CVVH pre-filter replacement
- CVVHD
- CVVHDF post-filter replacement
- K = Quf
- K = Quf / [1+(Quf/Qb)] ; correction factor
- K = Qd
- K = Quf + Qd ; if prefilter conside Quf with correction factor as in CVVH pre-filter
Generally a poison is not considered removable by HD ir HF if the protein binding is >80%, however there are exceptions…
1) some substances at toxic concentrations have saturated all protein binding sites, therefore there is a high proportion which is unbound and liable to HD/HF (i.e. salicilates or valproic acid)
2) some substances have a high dissociation quotent (loose binding with albumin) so once the unbound pool has been cleared more dissociates from albumin
3) states of hypoalbuminaemia
What are the major advantages and disadvantages of hemoperfusion vs hemodialysis?
Advantages:
- HP not influenced by molecular size or protein binding
Disadvantages:
- needs more systemic anticoagulation
- lower blood flow achievable due to high risk of hemolysis
- adsorbtion of platelets, WBC, calcium and glucose
- more costly and more difficult to get cartridges
- doesn’t correct metabolic derangements
- HP cartidges don’t absorb alchols or metals
HD is usually preferred to CRRT for poisoned patients, why?
What advantages can CRRT still bring in a poisoned patient?
- More rapid and efficient
- Slower blood flow advantageous in CV unstable patients, lower chances of rebound effect
Most common causes of acute on CKD in dogs
Mostly unknown, but suspected to be mainly inflammatory followed by pyelonephritis and ischemia.
Different from AKI where toxin exposure is a common feature
Most common causes of acute on CKD in cats
Mostly unknown but presumptive pyelonephritis and ischemic events
Short term prognosis vs long term prognosis indicators in ACKD in cats
Short term prognosis fair and related to serum phosphorus concentration
Long term prognosis poor (much worse than AKI) and related to IRIS stage and serum creatinine at time of discharge
Short term prognosis vs long term prognosis indicators in ACKD in dogs
Short term prognosis fair and related to respiratoru rate, serum creatinine and CK activity.
Long term prognosis poor (much worse than AKI) but no specific predictive factor identified.
