• Review the functions of the liver• Review diseases of the liver• Understanding neuro-psychologicalsymptoms associated with liver disease• Nutritional features of end stage liverdisease• Nutritional assement of end stage liverdisease• Nutritional management –ESPENGUIDELINES IN LIVER DISEASE
Functions of the Liver:• Largest organ in body, integral to mostmetabolic functions of body,• Only 10-20% of functioning liver isrequired to sustain life• Removal of liver will result in death within24 hours
• Main functions include:– Metabolism of CARBOHYDRATE, protein, fat– Storage/activation vitamins and minerals– Formation/excretion of bile– Steroid metabolism, detoxifier of drugs/alcohol– Action as (bacteria) filter and fluid chamber– Conversion of ammonia to urea• Gastrointestinal tract significant source of ammonia• Generated from ingested protein substances that aredeaminated by colonic bacteria• Ammonia enters circulation via portal vein• Converted to urea by liver for excretion
Understanding neuro-psychological symptomsassociated with liver diseaseAll neurological and psychological symptoms in patients with liverdisease that cannot be explained by presence of otherpathologies• Brain and nervous system damage secondary to severeliver dysfunction (most often chronic disease) resultingfrom failure of liver to remove toxins• Multifactorial pathogenesis with exact cause unknown• Symptoms vary from nearly undetectable, to coma withdecerebration– Characterized by various neurologic symptoms• Cognitive impairment• Neuromuscular disturbance• Altered consciousness• Reversible syndrome
Pathogenesis Theories• Endogenous Neurotoxins– Ammonia– Mercaptans– Phenols• Increased Permeability of Blood-Brain Barrier• Change in Neurotransmitters and Receptors– GABA– Altered BCAA/AAA ratio• Other– Zinc defficiency
Neurotoxic Action of Ammonia• Readily crosses blood-brain barrier• Increased NH3 = increased glutamate– α-ketoglutarate+NH3+NADH→glutamate+NAD– glutamate+NH3+ATP→glutamine+ADP+Pi• As a-ketoglutarate is depleted TCA cycle activity halted• Increased glutamine formation depletes glutamate storeswhich are needed by neural tissue– Irrepairable cell damage and neural cell death ensue.– In liver disease, conversion of ammonia to urea andglutamine can be reduced up to 80%
False Neurotransmitter Hypothesis• Liver cirrhosis characterized by alteredamino acid metabolism• Increased Aromatic Amino Acids in plasma andinflux in brain• Decrease in plasma Branched Chain Amino Acids• Share a common carrier at blood-brain barrier• DECREASE BCAAs in blood may result inINCREASE AAA transport to brain
• AAA are precursors to neurotransmittersand elevated levels result in shunting tosecondary pathways
Change In Neurotransmitters and Receptors• BRANCH CHAIN AMINOACID.• Fischer and colleagues, published their‘‘unifiedhypothesis on the pathogenesis ofHE’’ based on the observation that duringhepatic failure, plasma levels of BCAAdecreased and the AAA increased, DUETO increased BCAA catabolism in muscleand decreased AAA breakdown in thefailing liver.
• A reduction in the insulin/glucagon ratiowas hypothesized to play a key role indisturbing the balance between anabolismand catabolism.• Give rise to a decrease in the BCAA/AAAratio, which was called the Fischer-ratio(BCAA/AAA ratio).
The increase in plasma AAA incombinationwith an increased blood brain barrierpermeability for neutral amino acids hasbeen suggested to contribute to anincreased influx of AAA in the brain,because they compete for the sametransporter (large neutral amino acidtransporter). This, inturn, would lead toimbalances in neurotransmitter synthesisand accumulation of falsneurotransmitters,such as octopamine in thebrain, whichmay contribute to HE
• hyperammonemia during liverfailure, ammonia isdetoxified by alternative pathways, the mostimportant of which, although essentiallytemporary, is the formation of glutamine fromammonia and glutamate maInly in muscle &brain.• In muscle BCAA transaminate with a-ketoglutarate in the BCAA transferasereactions ,yielding glutamate, explaining whyhyperammonemia may contribute to low plasmaBCAA
• coupling of ammonia to glutamate in theglutaminsynthetase reaction as an alternativeammonia detoxification route,• glutamine is exported from muscle andbrain.The increased cerebral release ofglutamine in this hypothesis was thought tofacilitate the rapid exchange of glutamine forneutral amino acids, notably the AAA, by thelarge neutral amino acid carrier- This increasedinflux of AAA in the brain would raise theavailability of precursors for neutrotransmitters.
• BCAA levels are crucially determined bynutritional factors, whereas AAA levelsappear to depend much more upon intacthepatic metabolism.
Increase Permeability of Blood-Brain Barrier• Astrocyte (glial cell) volume is controlled byintracellular organic osmolyte• Organic osmolyte is glutamine.• glutamine levels in the brain result in volumeof fluid within astrocytes resulting in cerebraledema (enlarged glial cells)• Neurological impairment– N=Normal Astrocytes– A=Alzheimer type II astrocytes– Pale, enlarged nuclei– characterisic of HE
Nutritional Assessment ofpatients with ESLD Weight? Weight history? Protein markers of nutritional status? Descriptive history of wasting? Skinfolds? Intake? Appetite?
Assement…SGA for patients with liver disease .. Anthropometry Food history Nausea Anorexia Taste changes Diarrhoea Early satiety Functional capacity Grip strength
Daily energy expenditure1) predictive equation;-harris benedictequation( based on sex,ideal body wt,height).• Men: BMR = 66 + ( 13.7 x wt,kg ) + ( 5 x ht inch ) - ( 6.7x age in year )• Women: BMR = 655 + ( 9.6 x wt,kg ) + ( 1.8 x ht inch )- ( 4.7 x age in years )
• BEE(KCAL/DAY)- 25 x WT IN KG• To allow the thermal effect of food intakethe BEE multiplied by 1.2 to derive theresting energy expenditure-is in restingtate but not on fasted state.• In hypermetabolic condition –• Mild stress-BEEx1.2• Mod stress-BEEx1.4• Severe stress –BEEx1.6
• 2) indirect calorimetry.It is impossibel to mesure metabolic heatproduction in clinical practise, themetabolic energy expenditure is mesuredindirectly by mesuring whole body vo2 andvco2,technique called indirect calorimetry.
• ESPEN Guidelines on Enteral Nutrition:Liver disease
;NUTRION IN ALCOHOLIC HEPATITISsubject recommendation gradegeneral Use simple bedside methods such as theSubjectiveGlobal Assessment (SGA) or anthropometryto identify patients at risk of undernutrition.Recommended energy intake: 35–40 kcal/kg BW/dRecommended protein intake: 1.2–1.5 g/kgBW/dCccapplication Use supplementary enteral nutrition when patientscannot meet their caloric requirements throughnormal food.In general, oral nutritional supplements arerecommended.A
subject recommendation geradroute Use tube feeding if patients are not able to maintainadequate oral intake (even when oesophagealvarices are present)PEG placement is associated with a higher risk ofcomplications and is not recommendedACType offormulaWhole protein formulae are generallyRecommended.Consider using more concentrated high-energyformulae in patients with ascites.Use BCAA-enriched formulae in patients withhepatic encephalopathy arising during enteralnutrition.CCA
nutrition in liver cirrhosissubject recommendation gradeGeneral Use simple bedside methods such as the SubjectiveGlobal Assessment (SGA) or anthropometry toidentify patients at risk of undernutrition.Recommended energy intake: 35–40 kcal/kgBW/dRecommended protein intake: 1.2–1.5 g/kgBW/dCCCapplication Use supplementary enteral nutrition when patientscannot meet their caloric requirements throughnormal food.In general, oral nutritional supplements arerecommended.AA
route Use tube feeding if patients are not able to maintainadequate oral intake (even when oesophagealvarices are present)PEG placement is associated with a higher risk ofcomplications and is not recommendedAcType offormulaWhole protein formulae are generallyrecommended.Consider using more concentrated high-energyformulae in patients with ascites.Use BCAA-enriched formulae in patients withhepatic encephalopathy arising during enteralnutrition.The use of oral BCAA supplementation can improveclinical outcome in advanced cirrhosisCCAB
Nutrition in transplantation ANDSURGERY .surgerySUBJ RECOMME.. GRADEpreoperative Follow recommendations for cirrhosis. Bpostoperative Initiate normal food/enteral nutrition within12–24 h postoperatively.Initiate early normal food or enteral nutrition afterother surgical proceduresBroutepreop Follow recommendations for cirrhosis.postop Use nasogastric tubes or catheter jejunostomy forearly enteral nutrition.bFORMULA-PREOPFollow recommendations for cirrhosis.POSTOP Whole protein formulae are generallyrecommended.In patients with ascites prefer concentrated highenergy formulae for reasons of fluid balance.Use BCAA-enriched formulae in patients withhepatic encephalopathy arising during enteralnutrition.CCA
OUTCOME-PREOPAn improvement of perioperative mortality orcomplication rate by preoperative tube feeding ororal nutritional supplements has not yet beenshowN.OUTCOME-POSTOPEarly normal food or enteral nutrition isrecommended for transplant and surgery patientswith LC in order to minimise perioperative—inparticular infectious—complications.
NUTRTION IN ALCOHOLICSTETOHEPATITISSUBJECT RECOMMEN.. GRADEGENERAL Use simple bedside methods such as the SubjectiveGlobal Assessment (SGA) or anthropometry to identifypatients at risk of undernutrition.Start PN immediately in moderately or severelymalnourished ASH patients, who cannot be fedsufficiently either orally or enterally.Give i.v. glucose (2–3 g kg1 d1) when patients have toabstain from food for more than 12 h.Give PN when the fasting period lasts longer than 72 h.CACCENERGY Provide energy to cover 1.3REE .Give glucose to cover 50–60 % of non-protein energyrequirements.Use lipid emulsions with a content of n-6 unsaturatedfatty acids ..CCC
AMINOACIDSProvide amino acids at 1.2–1.5 g kg1 d CMICRONUTRIENTGive water soluble vitamins and trace elements dailyfrom the first day of PN.Administer vitamin B1 prior to starting glucose infusionto reduce the risk of Wernicke’s encephalopathyCCMONITORINGEmploy repeat blood sugar determinations in order todetect hypoglycemia and to avoid PN relatedhyperglycemia.Monitor phosphate, potassium and magnesium levelswhen refeeding malnourished patients.CC
IN LIVER CIRRHOSISSUBJECT RECOMMEN.. GRADEGENERAL Start PN immediately in moderately or severelymalnourished cirrhotic patients, who cannot be fedsufficiently eitherorally or enterally.Give i.v. glucose (2–3 g kg1 d1) when patients haveto abstain from food for more than 12 h.Give PN when the fasting period lasts longer than72 h.Consider PN in patients with unprotected airwaysand encephalopathy when cough and swallowreflexes are compromised.Use early postoperative PN if patients cannot benourished sufficiently by either oral or enteral route.After liver transplantation, use early postoperativenutrition; PN is second choice to EN.CACCCA
ENERGY Provide energy to cover 1.3 x REEGive glucose to cover 50 % - 60 % of non-proteinenergy requirements.Reduce glucose infusion rate to 2–3 g kg1 d1 in caseof hyperglycemia and use consider the use of i.v.insulin.Use lipid emulsions with a content of n-6 unsaturatedfatty acids lower than in traditional pure soybean oilemulsionsCCCAMINOACIDSProvide amino acids at 1.2–1.5 g kgIn encephalopathy III or IV, consider the use ofsolutions rich in BCAA and low in AAA, methionineand tryptophaneCA
MICRONUTRIENTGive water soluble vitamins and trace elements dailyfrom the first day of PN.In alcoholic liver disease, administer vitamin B1 priorto starting glucose infusion to reduce the risk ofWernicke’sencephalopathyCCMONITORINGEmploy repeat blood sugar determinations in order toavoid PN related hyperglycemia.Monitor phosphate, potassium and magnesium levelswhen refeeding malnourished patientsAC
IN ACUTE LIVER FAILUREGENERAL Commence artificial nutrition when patient is unlikely toresume normal oral nutrition within the next 5–7 days.Use PN when patients cannot be fed adequately byEN.CCENERGY Provide energy to cover 1.3 REE.Consider using indirect calorimetry to measureindividual energy expenditure.Give i.v. glucose (2–3 g kg1 d1) for prophylaxis ortreatment of hypoglycaemia.In case of hyperglycaemia, reduce glucose infusionrate to 2–3 g kg1 d1 and consider the use of i.v.insulin.Consider using lipid (0.8 – 1.2 g kg1 d1) together withglucose to cover energy needs in the presence ofinsulin resistanceCCCCC
IN ACUTE LIVER FAILURESUBJ RECOMMEN GRADEAMINOACID In acute or subacute liver failure, provide amino acidsat 0.8–1.2 g kg1 d1.CMONITORINGEmploy repeat blood sugar determinations in order todetect hypoglycaemia and to avoid PN relatedhyperglycaemia.Employ repeat blood ammonia determinations in orderto adjust amino acid provision.CC
References• Cornelis H. C. Dejong,4* Marcel C. G. van de Poll,4Peter B. Soeters,4 Rajiv Jalan,5and Steven W. M. OldeDamink4, Aromatic Amino Acid Metabolism duringLiverFailure1–3.• ESPEN Guidelines on Parenteral Nutrition:Hepatology,Mathias Plauth a, Eduard Cabre´ b, BernardCampillo c, Jens Kondrup d, Giulio Marchesini e,TatjanaSchu¨ tz f, Alan Shenkin g, Julia Wendon h.• Current Theories on the Pathogenesis ofHepaticEncephalopathy (43770)DARRELDL. MOUSSEAUA NDROGERF . BUTTERWORT…
• Branched-chain amino acids increase arterial bloodammonia in spite ofenhanced intrinsic muscle ammoniametabolism in patients with cirrhosisand healthysubjects,Gitte Dam,1 Susanne Keiding,1,2 Ole LajordMunk…• ESPEN Guidelines on Parenteral Nutrition: Intensivecare,Pierre Singer a, Mette M….• ESPEN Guidelines on Enteral Nutrition: Liverdisease$M. Plautha,, E. Cabre´b, O. Riggioc, M. Assis-Camilod,