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Transcript of liver support systems
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Hanan Fathy
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Toxins: Bile acids
Bilirubin
Prostacyclins
Nitric oxide
Indol / Phenol-
Metabolites
Toxic fatty acids
Thiols Digoxin/Diazepam-
like subs.
...
Ammonia
Lactate
Further liver damage
via vicious cycle:
necrosis/apoptosis !!!
Brain Function Kidney Function
Cardiovascular Tone Bone Marrow Activity
Liver failure - endogenous
intoxication
OngoingOngoing
ImbalanceImbalance
ofof
water-solublewater-soluble
andand
non-solublenon-solublesubstancessubstances
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Main Indication groups for liver
support systems
1-Acute liver failure
2-Acute decompensation on chronic liver disease Complicated by progressive jaundice
Complicated by hepatic encephalopathy Complicated by renal dysfunction
3-Intractable pruritus in cholestasis
4-Acute intoxication or overdose with substances potentiallybound to albumin
5-Other indications Acute hepatic failure after major hepatectomy After liver transplantation
Primary non-function or primary dysfunction of the graft Acute decompensation of the graft
Secondary liver failure or multi-organ failure
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Liver support therapy
Balance ofwater-solublesubstances
Balance ofprotein bound
substances
Dialysis Albumin Dialysis
Water based human body
Diffusion
Plasma exchange
(unselective)
Binding site
related distribution
Filtration
(unselective)
water-solubletoxins
(free)
non water-solubletoxins
(protein bound)
Toxin removal
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Liver support systems can be divided into two
main groups:
Non biologic liver support.
Biologic liver support.
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Millis JM and Losanoff JE (2005) Technology Insight: liver support systemsNat Clin Pract Gastroenterol Hepatol2: 398405 doi:10.1038/ncpgasthep0254
Biologic liver support
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Millis JM and Losanoff JE (2005) Technology Insight: liver support systemsNat Clin Pract Gastroenterol Hepatol2: 398405 doi:10.1038/ncpgasthep0254
Nonbiologic liver support
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Molecular Adsorbent Recycling System (MARS)
Removal of soluble and protein-bound substances
against albumin-rich dialysate.
Fractionated plasma separation and adsorption(Prometheus).
Fractionation of plasma and detoxification of albumin
by adsorption.
Single-pass albumin dialysis.
One-pass dialysis against albumin solution.
Liver Support Systems
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Non-Biological Filtration
Techniques
Albumin dialysis pumps the blood out of thebody and into a plastic tube filled with hollow
fibers made of a membrane that has beencoated with albumin.
On one side of the fiber's membrane is theblood; on the other, a dialysis solution
containing more albumin.
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Non-Biological Filtration
Techniques
The toxins on the albumin in the patient's blood
are attracted to the albumin on the membrane,
which is "stickier" because it has more room formolecules to attach.
Then, the albumin on the membrane passes the
toxins along to the albumin in the solution as it
flows by.
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Non-Biological Filtration
Techniques
Meanwhile, smaller toxin molecules thatdon't stick to albumin flow through the
membrane's tiny pores into the less-concentrated dialysis solution.
The patient's own albumin, too large to fit
through the membrane's pores, returns tothe body with the blood.
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P
atie
nt
High
-f
lux
D
Hig
h-flux
DHigh
-f
lux
D
High
-f
lux
DFiltrate
recirculation
circuit
Low-flux D
Albumin20%
600ml
MARS
MARSMARS
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The MARS principle
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The MARS membrane
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MARS Absorber cartridges
Activated charcoal
column
(diaMARS AC250)
Anion-exchanger
resin column
Liver support therapy
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Among the toxins that MARS can remove are:
Bile acids
Bilirubin
Aromatic aminoacidsPhenols
Mercaptans
Dioxin like substancesTryptophan
Liver support therapy
Short and middle chain fatty
acids Benzodiazepine like
substances Nitric oxide Ammonia Creatinine Urea
Copper Iron
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20
Prometheus Circuit
Hemodialysis and liver dialysis (2 systems in 1)
Prometh 01column contains highly
porousneutral resinfor the removal
of albumin bound toxins such as
bile acids, aromatic Acids &
phenolic substances. The Inner part
is highly porous & offers a huge
surface area with multiple binding
sites to toxins
Prometh 02column contains anion
exchange resins with spongy inner
portions to increase surface area. It
containspositively charged ligands
capable of binding negatively charged
substances ex: unconjugated bilirubin
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Liver Support Therapy: Prometheus Machines
PrometheusCitrate
PrometheusHeparin
Prometheus: Hemodialysis & Liver Dialysis
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Toxin Elimination
Toxins Damage Elimination
Ammonia Hepat. Encephalopathy Dialysis
Creatinin, urea Kidney failure (HRS) Dialysis
Bilirubin Hepat. Encephalopathy Dialysis/02Benzodiazepine Hepat. Encephalopathy prometh01
Arom. amino acids Hepat. Encephalopathy prometh01
Bile acids Pruritus prometh01
Nitrogen oxide Hemodyn. Instability prometh 01Indols, phenols Hepat. Encephalopathy prometh01
waterwater
solublesoluble
albuminalbumin
boundbound
The Livers Poison Cabinet
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In-vivo comparisons of both systemsshowed :
significantly higher extraction capacities
for protein-bound and water-solublesubstances under Prometheus thanunder MARS treatment.
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Continuous Veno- Venous Single Pass
Albumin Haemodiafiltration ( SPAD)
Albumin 20%
. 70 ml/h
Roler pump 1
Filtrate pump
Substitute
400ml/h
Highfluxfilter
Waste
800ml/h
Substitute
330ml/h
Roler pump 2
Substitute pump
Blood pump
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SPAD :
- lowers effectively bilirubin, bile acids undammonium in ALF
- reduces hepatic encephalopathy
- is well tolerated in case of SPAD System pre-fillingeven in a catecholamine dependant patient
- stabilizes children prior to LTX and is helpful forbridging to transplantation.
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Continuous Veno- Venous Single Pass
Albumin Haemodiafiltration ( SPAD)
Albumin 20%
. 70 ml/h
Roler pump 1
Filtrate pump
Substitute
400ml/h
Highflu
xfilter
Waste
800ml/h
Substitute
330ml/h
Roler pump 2
Substitute pump
Blood pump
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