Download Hepatic Failure: Role for biochemists and nutrition experts

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Volume 1; I s s ue 1; Januar y - Mar ch 2002
S h or t Com m u n icat ion
H epat ic F ai lu r e: R ole f or bioch em is t s an d n u t r it ion ex per t s
An an t h N
Depar tment of B iochemis tr y, Center for B as ic S ciences , Mangalor e - 575004 , I NDI A.
Email: gmcs f@ oper amail.com
Ci t at i on : Ananth N. Hepatic Failur e: Role for biochemis ts and nutr ition ex per ts . Online J Health Allied
S cs . 2002; 1: 2
U R L : http: //www.oj has .or g/is s ue1/2002- 1- 2.htm
Open Acces s Ar ch i ve: http: //cogpr ints .ecs .s oton.ac.uk/view/s ubj ects /OJHAS .html
T he liver
is the lar ges t gland of the human body.
S ometimes r efer r ed to as the " gr eat chemical
factor y" of the body, the liver cr eates , r egulates , and
s tor es a var iety of s ubs tances us ed by the
gas tr ointes tinal s ys tem and it s er ves a number of
impor tant diges tive functions . T he liver als o plays a
maj or r ole in the r egulation of blood s ugar . T he liver
s ynthes izes dis s olves , and s tor es amino acids ,
pr otein, and fat. I t s tor es s ever al impor tant vitamins
like B - 12 and Vitamin A. T he liver als o dis pos es of
cellular was te and br eaks down har mful s ubs tances
like alcohol, dis pos ing them into the bile.
Acute inj ur y to the liver due to caus es s uch as
hepatitis , tox ins , encephalopathy and chr onic liver
failur e ar e well- documented caus es of a ver y near ly
fatal manifes tation ter med " Hepatic Failur e" (HF).
Owing to the multitude of functions that the or gan
per for ms , the management and tr eatment of HF
pos es a tr ue challenge to a clinician and a biochemis t
/ nutr ition ex per t put together . Pinning down the
under lying caus e with a batter y of tes ts and
inves tigations as s is ts the clinician for diagnos is and
mos tly the pr ognos is of the condition, s ince mor tality
r ate is ver y high in HF.
S imultaneous ly, a biochemis t / nutr ition ex per t
needs to think on the lines of S uppor tive Nutr itional
T her apy. S ince the liver eventually metabolizes all
nutr ients
adminis ter ed either
par enter ally
or
enter ally, HF pos es a for midable challenge. I t is bas ic
to r eview br iefly the metabolic der angements in HF
befor e cons ider ing Nutr itional S uppor t. Mos t of s uch
changes ar e mediated by cytokines whos e r oles have
yet to be clear ly defined.
1.
Hyper ins ulinemia, a cons equence of decr eas ed
hepatic clear ance r es ults in hyper glycemia and
per ipher al ins ulin r es is tance.
2.
3.
4.
5.
6.
Decr eas ed s ynthes is of I GF 1 caus es ex ces s ive
pr otein catabolis m and a r educed glycogenes is .
A low ins ulin: glucagon r atio changes the nor mal
" milieu inter ior " of the cells .
Lipid metabolis m r epr es ents an acceler ated
s tate of s tar vation and leads to depletion of fat
s tor es and es s ential fatty acid deficiency.(1)
Decr eas ed activity of hepatic lipopr otein lipas e
and mild hyper tr iglycer idemia ens ue.
Pr otein s ynthes is is decr eas ed as is tr ue with
ever y hepatocellular dis or der . An incr eas e in
ammonia pr oduction due to glutamine ox idation
(2) may aggr avate encephalopathy, bacter ia
contr ibuting to ver y ins ignificant amounts of
ammonia.
HF has a well- defined r elation with ammonia levels
and neur otr ans mitter s . (3) Ammonia metabolis m
pr imar ily occur s in the hepatic tis s ue and s econdar ily
in the mus cle tis s ue. Due to mus cle was ting in HF,
ammonia metabolis m in the mus cle is diminis hed
and ex ces s ammonia cr os s es the blood- br ain bar r ier .
T he ammonia thus having enter ed the cr anial s pace
combines with glutamic acid r es ulting in the
for mation of Glutamine, a r eaction catalys ed by the
enzyme Glutamine s ynthetas e. Glutamine then acts
as a pr edis pos ing factor to the cer ebr al edema that
follows . (4)
T he biological amines pr oduced as a r es ult of
decar box ylation of s elected amino acids s uch as
tyr os ine,
tr yptophan
ar e
the
phys iologically
s ignificant neur otr ans mitter s . However , amines s uch
as phenylethylamine, tr yptamine which ar e not the
" tr ue" neur otr ans mitter s als o r es ult fr om the pr oces s
and ar e nor mally clear ed by the liver . I n HF, thes e
" fals e" neur otr ans mitter s ar e not clear ed by the liver
and get acces s to the br ain.
T hus , bear ing all thes e metabolic der angements in
mind, a biochemis t mus t ins titute a Nutr itional
S uppor t to s uit the delicate s ys tem. Pr otein ener gy
malnutr ition is common in HF (5) and mor e s o with a
his tor y of alcoholis m. I n all s uch cas es , appr opr iate
nutr itional inter vention and s uppor t s hould be
ins tituted as ear ly as pos s ible. Cor r ections for
hemodynamic par ameter s and electr olytes need to
be paid equal attention too.
Route of adminis tr ation s hould not pos e a pr oblem if
the phys iology of the gut is nor mal. However , a
combination of r outes s uch as enter al, or al and
par enter al may be us ed.
Guidelines for Nutr itional S uppor t in HF ar e defined
by the Eur opean S ociety for Par enter al and Enter al
Nutr ition (ES PEN). (6) Pr otein r equir ements ar e
incr eas ed in HF (7) and mus t be ins tituted as a par t
of the Nutr itional S uppor t along with neomycin which
helps to lower the ammonia bur den by r educing the
activity of the s ynthetas e. (8) B r anched chain amino
acids mus t be pr ovided as a par t of the
s upplementation and the pr otein feed could r ange
fr om 0.6 g / kg body weight upto 1.5 / kg body
weight depending on the gr ade of HF.
Deficiencies of both water and fat- s oluble vitamins
ar e known. T hough commer cial vitamin s upplements
may pr ovide s uppor t, adequacy may s till be
ques tionable. T hiamin and Vitamin K deficiency ar e
well documented. T hiamin deficiency leads to lactic
acidos is and may manifes t as conges tive hear t
failur e.(9) A dos e of up to 50 mg per day has been
r ecommended.
HF has been as s ociated with Z inc deficiency.(10)
Par enter al s upplementation up to 600 mg of s ulfate
s alt /day has been found to be appr opr iate. Other
tr ace elements that need to be s upplemented ar e
S elenium, Copper and Manganes e.
With r efer ence to electr olytes , mild s odium
r es tr iction has been r ecommended. Adequate
Potas s ium, Magnes ium and Phos phates have to be
pr ovided.
Calor ie r equir ements have been es timated at 25- 30
non- pr otein Kcal/kg/day. Only car bohydr ate s our ces
mus t be us ed for par enter al nutr ition. Adminis tr ation
of intr avenous fats have als o been attempted.(11)
Enter al r oute for fats is not r ecommended s ince
malabs or ption is common in HF.
A car eful follow- up for s uch cas es is abs olutely
es s ential. S er um tr iglycer ide es timations need to be
per for med
r egular ly
alongs ide
per iodic
deter minations
of glucos e, Pr othr ombin time,
electr olytes and tr ace elements .
CON CL U S I ON
I n conclus ion, nutr itional s uppor t to HF patients is
challenging and r equir es ex per ience, s kill, car eful
planning and meticulous follow- up. I t is indeed an
attempt to r eplenis h the los t power of one of the
mos t vital or gans we pos s es s .
R E F E R E N CE S :
Cabr e, E, Abad- Lacr uz, A, Nunez, M.C etal:
T he r elation of plas ma polyuns atur ated fatty
acid deficiency with s ur vival in advanced liver
cir r hos is : a multivar iate analys is . Am J Gas tr .
1993; 88: 718.
2. James , J.H, Jepps on, B ., Z ipar o, V. and
Fis her , J.E.: Hyper ammonemia, plas ma
aminoacid imbalance and blood- br ain
aminoacid tr ans por t: a unified theor y of
por tal- s ys temic encephalopathy. Lancet.
1979; 2: 772.
3. Hawkins , R.A., Mans , A.M.,: B r ain metabolis m
in encephalopathy caus ed by
hyper ammonemia. Adv Ex p Med B iol. 1994;
368: 11.
4. T akahas hi, H., Koehler , R., Br udiolos , S .W.,
and T r ays tman, R.J.: I nhibition of br ain
glutamine accumulation pr events cer ebr al
oedema in hyper ammons emic r ats . Am J
Phys iol. 1991; 261: H 825.
5. Mar s ano, L. and McClain, C.J.: Nutr ition and
alcoholic liver dis eas e: JPEN, 15: 337, 191.
6. Plauth, M., Mer li, M., Kondr up, J., etal: ES PEN
guidelines for nutr ition in liver dis eas e and
tr ans plantation. Clin Nutr . 1997; 16: 43.
7. S war t, G.R., van den Ber g, J.W.O.,
Wattinema, J.L., etal: Elevated pr otein
r equir ements in cir r hos is of the liver
inves tigated by whole body pr otein tur nover
s tudies . Clin S ci. 1988; 75: 101.
8. Hawkins , R.A., Jes s ey, J., Mans , A.M., Cheid,
A. and De Jos eph , M.R.: Neomycin r educes
the intes tinal pr oduction of ammonia fr om
glutamine. Adv Ex p Med B iol. 1995; 368: 125.
9. Les lie, D., Gher ghiade, M.: I s ther e a r ole for
thiamine s upplementation in the management
of hear t failur e? Am Hear t J. 1996; 131: 124850.
10. McClain, C.J., Mar s ano, L., B ur k, R.F. and
B acon,B .: T r ace elements in liver dis eas e.
S emin Liv Dis . 1991; 18: 321.
11. Mus cur atoli, M., Cangiano, C., cas cino, A.
etal: Ex ogenous lipid clear ance in
compens ated liver cir r hos is , JPEN. 1986;
10: 599.
1.