HEPATIC FAILUREHEPATIC FAILURE

DR.M.H.MumtazDR.M.H.Mumtaz

TopicsTopics

• AnatomyAnatomy• HistologyHistology• Liver FunctionsLiver Functions• Liver Function TestsLiver Function Tests• Liver FailureLiver Failure• Management in ICUManagement in ICU

ANATOMYANATOMY

Wt . 1.8 - 2 KgWt . 1.8 - 2 Kg Blood supply = 25 % COBlood supply = 25 % CO Topography = 2 Lobes subdivided into lobules Topography = 2 Lobes subdivided into lobules

Rt Lobe =have 2 suspended LobesRt Lobe =have 2 suspended Lobes

Caudate LobeCaudate Lobequadrate Lobequadrate Lobe

Liver Blood FlowLiver Blood Flow

Total = 1100 -1800 ml Total = 1100 -1800 ml / / min 25min 25 % % COCO Hepatic artery = 30 – 40 %Hepatic artery = 30 – 40 %

= O2 supply = 40 - 55 %= O2 supply = 40 - 55 %

= Saturation = 98 %= Saturation = 98 %

= flow = = flow = sphincteric mechanismsphincteric mechanism

Liver Blood FlowLiver Blood Flow

Hepatic Portal veinHepatic Portal vein= 70 % B. flow= 70 % B. flow=50 - 60 % O2 supply=50 - 60 % O2 supply= po2 = 50 mm Hg= po2 = 50 mm Hg= blood velocity = 9 cm/sec= blood velocity = 9 cm/sec

Hepatic arterio-venous reciprocityHepatic arterio-venous reciprocity

Liver Blood FlowLiver Blood Flow

Blood FlowBlood Flow

1.1. PCO2PCO22.2. HepatitisHepatitis3.3. Supine PostureSupine Posture4.4. FoodFood5.5. DrugsDrugs

• Beta stimulantsBeta stimulants• PhenobarbitonePhenobarbitone• Enzyme inducersEnzyme inducers

Blood FlowBlood Flow

1.1. IPPV + PEEPIPPV + PEEP2.2. SurgerySurgery3.3. PCO2 , HypoxiaPCO2 , Hypoxia4.4. Upright postureUpright posture5.5. CirrhosisCirrhosis6.6. DrugsDrugs

• alpha stimulantsalpha stimulants• Beta blockersBeta blockers• Ganglion blockersGanglion blockers• RanitidineRanitidine• PitressinPitressin• AnaestheticsAnaesthetics

HistologyHistology

zone 1 - receives blood with spo2zone 1 - receives blood with spo2

zone 2 - intermediatezone 2 - intermediate

zone 3 - receives blood with spo2zone 3 - receives blood with spo2

Important Liver FunctionsImportant Liver Functions

A.A. Carbohydrate MetabolismCarbohydrate Metabolism

1. Glycogen synthesis1. Glycogen synthesis

2. Glycogenolysis2. Glycogenolysis

3. Gluconeogenesis3. Gluconeogenesis

Important Liver FunctionsImportant Liver Functions

B.B. Lipid MetabolismLipid Metabolism1.1. Synthesis of LipoproteinsSynthesis of Lipoproteins

• PhospholipidsPhospholipids• CholesterolCholesterol• Endogenous TriglyceridesEndogenous Triglycerides

2.2. Excretion of breakdown products of Excretion of breakdown products of cholesterolcholesterol

3.3. Ketone synthesisKetone synthesis

Important Liver FunctionsImportant Liver Functions

C.C. Protein SynthesisProtein Synthesis

D.D. Vitamin .D metabolismVitamin .D metabolism

E.E. Vitamin A, B, B12. stored in liverVitamin A, B, B12. stored in liver

F.F. Iron storeIron store

G.G. Excretion & DetoxicationExcretion & Detoxication

H.H. Reticuloendothelial functionReticuloendothelial function

Liver Function TestsLiver Function Tests

A.A. Static TestsStatic Tests

B.B. Dynamic TestsDynamic Tests

Liver Function Liver Function ((Static )Static )TestsTests

Liver cell damageLiver cell damage1.1. TransaminasesTransaminases2.2. Lactate dehydrogenaseLactate dehydrogenase

Liver cell dysfunctionLiver cell dysfunction1.1. Serum ProteinsSerum Proteins2.2. Coagulation factors - PT, APTTCoagulation factors - PT, APTT3.3. Serum BilirubinSerum Bilirubin

Biliary Tract obstructionBiliary Tract obstruction1.1. Alkaline PhosphataseAlkaline Phosphatase2.2. Gama-glutamyl TransferaseGama-glutamyl Transferase3.3. BilirubinBilirubin

Tests Indicating aetiologyTests Indicating aetiology

ROLE OF VIT KROLE OF VIT K

LIVERLIVER ----------VIT. K ----------VIT. K

WARFARINWARFARIN ------- -------gamma glutamyl carboxylasegamma glutamyl carboxylase

ADDSADDS

carboxyl group to glutamic acid residuecarboxyl group to glutamic acid residue ONON

Factors, Factors, 22ndnd,7,7thth,9,9thth & 10 & 10thth. Proteins S,C,&Z. Proteins S,C,&Z

( activation)( activation)

PROTHROMBIN TIME(PT)PROTHROMBIN TIME(PT)

HEPARINESHEPARINES

ANTITHROMBINSANTITHROMBINS(SERINE PROTEASE INHIBITOR)(SERINE PROTEASE INHIBITOR)

DEGRADEDEGRADE

THROMBIN,F9a, F10a,F12a ( serine proteins)THROMBIN,F9a, F10a,F12a ( serine proteins)

HEPARIN HEPARIN increase adhesion of antithrombins to factors increase adhesion of antithrombins to factors

Functional Functional ( ( Dynamic) TestsDynamic) Tests

1.1. Impaired Lactate clearance (lactate level)Impaired Lactate clearance (lactate level)

2.2. Clearance of organic substancesClearance of organic substances• Anionic dye – Indocyanine green (ICG)Anionic dye – Indocyanine green (ICG)

3.3. Formation of metabolitesFormation of metabolites• Monoethylglycinxylidid from lidocain (MEGX)Monoethylglycinxylidid from lidocain (MEGX)

Topology of Liver DamageTopology of Liver Damage

1.1. Diffuse Parenchymal damageDiffuse Parenchymal damage

2.2. Periportal damagePeriportal damage

3.3. Pericentral damagePericentral damage

Response to injuryResponse to injury

1.1. NecrosisNecrosis

2.2. DegenerationDegeneration

3.3. SteatosisSteatosis

4.4. RegenerationRegeneration

5.5. InflammationInflammation

6.6. FibrosisFibrosis

ETIOLOGICAL FACTORSETIOLOGICAL FACTORS

1.1. NON . INFECTIOUSNON . INFECTIOUS• AlcoholAlcohol• Drug relatedDrug related• Reyes’ SyndromeReyes’ Syndrome• PregnancyPregnancy

2.2. INFECTIOUS DAMAGEINFECTIOUS DAMAGE• FungalFungal• ProtozoalProtozoal• MalariaMalaria• ParasitesParasites• Liver abscessLiver abscess

Aetiology 3.Aetiology 3. Viral InfectionsViral Infections

a. Systemic Viral infectiona. Systemic Viral infection

• Infectious mononucleosisInfectious mononucleosis

• cytomegaloviruscytomegalovirus

• Herpes virusHerpes virus

• In children ( rubella, adenovirus enterovirus)In children ( rubella, adenovirus enterovirus)

Aetiology, 3. Viral infectionsAetiology, 3. Viral infections

b. Hepatotropic Virusesb. Hepatotropic Viruses Hepatitis A virus (HAV)Hepatitis A virus (HAV) Hepatitis B virus (HBV)Hepatitis B virus (HBV) Hepatitis C virus (HCV)Hepatitis C virus (HCV) Delta Hepatitis virus (HDV)Delta Hepatitis virus (HDV) Hepatitis E virus ( HEV )Hepatitis E virus ( HEV ) Others – ( F,G…. ? )Others – ( F,G…. ? )

4.4. Inborn Errors of metabolismInborn Errors of metabolism

• Primary HaemochromatosisPrimary Haemochromatosis

• Wilsons’ DiseaseWilsons’ Disease

• Alpha – 1 – Antitrypsin deficiencyAlpha – 1 – Antitrypsin deficiency

5.5. TumoursTumours

• BenignBenign

• MalignantMalignant

LIVER FAILURE MANIFESTATIONSLIVER FAILURE MANIFESTATIONS

a.a. Hepatic ManifestationsHepatic Manifestations• JaundiceJaundice• CoagulopathyCoagulopathy

b.b. Extrahepatic ManifestationsExtrahepatic Manifestations• EncephalopathyEncephalopathy• Hepato-renal SyndromeHepato-renal Syndrome• Susceptibility to infectionsSusceptibility to infections

MANAGEMENT IN ICUMANAGEMENT IN ICU

General Intensive CareGeneral Intensive Care• Enteral nutritionEnteral nutrition• Stress ulcer prophylaxisStress ulcer prophylaxis• Glucose HomeostasisGlucose Homeostasis• Antibiotic prophylaxis / SDDAntibiotic prophylaxis / SDD• Control Intracranial HypertensionControl Intracranial Hypertension• AlbumenAlbumen• Vasopressor for HRSVasopressor for HRS

MANAGEMENTMANAGEMENT

Specific Therapy- AntidoteSpecific Therapy- Antidote

Monitoring by. PDR – ICGMonitoring by. PDR – ICG

Extracorporeal SupportExtracorporeal Support

Liver TransplantLiver Transplant

Hepatic EncephalopathyHepatic Encephalopathy

Toxic MetabolitesToxic Metabolites ammonia,glutamineammonia,glutamine ^ ICP^ ICP Ippv,Mannitol,HypothermiaIppv,Mannitol,Hypothermia Hypertonic salineHypertonic saline Vasopressors--caution Vasopressors--caution

Hepatorenal SyndromeHepatorenal Syndrome

1, Marked renal vasoconstriction 1, Marked renal vasoconstriction RBF decreasedRBF decreased GFR decreasedGFR decreased 2,Absence of histological changes2,Absence of histological changes 3,Preserved tubular renal function3,Preserved tubular renal function

HRS PathogenesisHRS Pathogenesis

Portal hypertension/Liver failurePortal hypertension/Liver failure

1, Increased level of ; NO, CO.1, Increased level of ; NO, CO.

2, Spanchnic arterial vasodilation2, Spanchnic arterial vasodilation

3,Low effective circulating volume3,Low effective circulating volume

4, Activation of systemic endogenous4, Activation of systemic endogenous

vasoconstrictorsvasoconstrictors

5, Svere renal vasoconstriction5, Svere renal vasoconstriction

HRS Diagnostic criteriaHRS Diagnostic criteria

Major criteriaMajor criteria CHF +Portal hypertensionCHF +Portal hypertension Low GFRLow GFR

Absence-Absence-shock,infection,drugshock,infection,drug dehydrationdehydration No improovement after,removal ofNo improovement after,removal of

diuretics, pv expansiondiuretics, pv expansion Proteinurea <500mg/dlProteinurea <500mg/dl

HRS Diagnostic criteriaHRS Diagnostic criteria

Minor criteriaMinor criteria

Urine volume<500ml/dUrine volume<500ml/d

Urine sod.excretion<10mmol/lUrine sod.excretion<10mmol/l

urine osmolality/plasma osm>1urine osmolality/plasma osm>1

No finding in urine sedimentNo finding in urine sediment

Natremia <130mmol/lNatremia <130mmol/l

All major criteria +a few minor to supportAll major criteria +a few minor to support

HRSHRS

TYPESTYPES

Type 1, Type 2Type 1, Type 2

Rapidly progressive---RF with out rapidly Rapidly progressive---RF with out rapidly

progressiveprogressive

Acute r.failure-------------Refractory ascitesAcute r.failure-------------Refractory ascites

HRSHRS

Precipitating eventsPrecipitating events

spontaneus bacterial peritonitisspontaneus bacterial peritonitis

paracentesis without plasma expanparacentesis without plasma expan

GIT haemorrhageGIT haemorrhage

Severe acute alcoholic hepatitisSevere acute alcoholic hepatitis

Unknown Unknown

HRS THERAPYHRS THERAPY

TIPSTIPS

(transjugular intravenous portosystamic s.)(transjugular intravenous portosystamic s.)

++

Albumin,vasoconstrictorsAlbumin,vasoconstrictors

MARSMARS

(molecular adsorbant recycling system)(molecular adsorbant recycling system)

New therapies -HRSNew therapies -HRS

Albumin+trlipressinAlbumin+trlipressin

Albumin+Midodrine+octreotideAlbumin+Midodrine+octreotide

Albumin+NoradrenalineAlbumin+Noradrenaline

Extracorporeal Liver SupportExtracorporeal Liver Support