hepatic failure dr.m.h.mumtaz. topics anatomyanatomy histologyhistology liver functionsliver...
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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
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