… … oh the failureoh the failureImogen KetchleyImogen Ketchley

Sam AndrewsSam Andrews

HistoryHistory

• 54 yr old54 yr old• MaleMale• Retired engineerRetired engineer• 1999 – Decompensated Alcoholic 1999 – Decompensated Alcoholic

Liver DiseaseLiver Disease• 2000 – Oesophageal Varices Banded2000 – Oesophageal Varices Banded

Presenting ComplaintPresenting Complaint

• JaundiceJaundice• Abdominal SwellingAbdominal Swelling• MalaiseMalaise

History of presenting History of presenting complaintcomplaint

• 3/52 – gradual onset and worsening 3/52 – gradual onset and worsening of presenting symptomsof presenting symptoms

• 1/52 – decreased urine output1/52 – decreased urine output• 1/52 – hyperpigmentation of urine1/52 – hyperpigmentation of urine• 4/7 diarrhoea (no blood, no mucus)4/7 diarrhoea (no blood, no mucus)• Stools soft and dark (on iron)Stools soft and dark (on iron)• No HaemetemesisNo Haemetemesis

Drug HistoryDrug History

• Frusemide – 40mg odFrusemide – 40mg od• Spironolactone – 50mg odSpironolactone – 50mg od

• FeSOFeSO4 4 – 200mg bd– 200mg bd

• Salbutamol – PRNSalbutamol – PRN• Multivitamins - bdMultivitamins - bd

Family/Social HistoryFamily/Social History• FH:FH:• No liver disease, malignancies or other No liver disease, malignancies or other

significant conditions.significant conditions.

• SH:SH:• Lives with wife in Colliers WoodLives with wife in Colliers Wood• Work: Chauffeur (previously an engineer)Work: Chauffeur (previously an engineer)• Smoker: 40 pack yrsSmoker: 40 pack yrs• Alcohol: “gave up drinking three years ago” Alcohol: “gave up drinking three years ago” • Previously 48 units/wk Previously 48 units/wk

On examinationOn examination

• CVS:CVS:• BP: 148/79 Pulse: 103 (regular) BP: 148/79 Pulse: 103 (regular) • Sats: 95% (on air) Sats: 95% (on air) • HS: I + II + 0HS: I + II + 0• Bilateral Pitting Oedema of ankles Bilateral Pitting Oedema of ankles

and lower calfand lower calf

• Resp: Resp: • Fine creps on left and right basesFine creps on left and right bases

Examination cont.Examination cont.• Abdo:Abdo:

• Spider NaeviSpider Naevi• JaundicedJaundiced• Gross ascitesGross ascites• Enlarged firm liver edgeEnlarged firm liver edge• No splenomegalyNo splenomegaly• Abdomen soft and non-tenderAbdomen soft and non-tender• Bowel sounds presentBowel sounds present• Extensive caput medusaExtensive caput medusa• Gynaecomastia present Gynaecomastia present

• Neuro:Neuro:• Grade 1 encephalopathyGrade 1 encephalopathy

Blood Results - April 2003Blood Results - April 2003

• Hb: Hb: 11.511.5 (13 - 18 g/dL)(13 - 18 g/dL)• WBC: 6.1 WBC: 6.1 (3.8 - 11x10(3.8 - 11x1099/L)/L)• Platelets: Platelets: 8383 (150 - 450x10(150 - 450x1099/L)/L)• MCV: MCV: 99.199.1 (78 - 96 FL)(78 - 96 FL)

U’s & E’s and LFT’s - April U’s & E’s and LFT’s - April 20032003

• Na: 137 Na: 137 (135 - 145 mmol/L)(135 - 145 mmol/L)• K: 3.9 K: 3.9 (3.5 - 4.7 mmol/L)(3.5 - 4.7 mmol/L)• Urea: 3.3 Urea: 3.3 (2.5 - 8.0 mmol/L)(2.5 - 8.0 mmol/L)• Creatinine: 67 Creatinine: 67 (60 -110 µmol/L)(60 -110 µmol/L)• Bilirubin: Bilirubin: 4646 (0-17 µmol/L)(0-17 µmol/L)• Alanine Transaminase: Alanine Transaminase: 4949 (5 - 40 IU/L) (5 - 40 IU/L)• Albumin: Albumin: 3030 (38-48 g/L)(38-48 g/L)• Gamma GT: Gamma GT: 227227 (0-60 IU/L)(0-60 IU/L)

Blood Results on Blood Results on Presentation 7/10/03Presentation 7/10/03

Hb – Hb – 12.312.3 (13-18 g/dL)(13-18 g/dL) WBC – WBC – 16.616.6 (3.8-11x10(3.8-11x1099/L)/L) Platelets – Platelets – 7777 (150-450x10(150-450x1099/L)/L) MCV – MCV – 106106 (78-96 FL)(78-96 FL)

U’s & E’s and LFT’sU’s & E’s and LFT’s7/10/037/10/03

• Na – Na – 126 126 (135-145 (135-145 mmol/L)mmol/L)

• K – 3.8 K – 3.8 (3.5-4.7 mmol/L)(3.5-4.7 mmol/L)• Urea – Urea – 15.215.2 (2.5-8.0 mmol/L)(2.5-8.0 mmol/L)• Creatinine – Creatinine – 369369 (60-110 µmol/L)(60-110 µmol/L)• Bilirubin – Bilirubin – 576576 (0-17 µmol/L)(0-17 µmol/L)• Alanine Transaminase – Alanine Transaminase – 9292 (5-40 IU/L)(5-40 IU/L)• Albumin – Albumin – 2121 (38-48 g/L)(38-48 g/L)• Gamma GT – Gamma GT – 167167 (0-60 IU/L)(0-60 IU/L)

Abdominal UltrasoundAbdominal Ultrasound

• Liver CirrhosisLiver Cirrhosis

• AscitesAscites

• Reversal of Portal Vein flowReversal of Portal Vein flow

• Normal kidney’sNormal kidney’s

In SummaryIn Summary

• 54 year old Male54 year old Male• 4 year history of Alcoholic Liver Disease4 year history of Alcoholic Liver Disease

• Main Problems:Main Problems:• Jaundice due to cirrhosisJaundice due to cirrhosis• Ascites due to decompensated liver Ascites due to decompensated liver

diseasedisease• Poor renal functionPoor renal function

Complications of CirrhosisComplications of Cirrhosis

• Ascites develops late in the course;Ascites develops late in the course;• Severe portal hypertensionSevere portal hypertension• Hepatic insufficiencyHepatic insufficiency• Poor survival: 50% mortality in 3 yearsPoor survival: 50% mortality in 3 years• Clear indication for liver transplantationClear indication for liver transplantation

• Systemic Haemodynamics + Renal Function:Systemic Haemodynamics + Renal Function:• Better predictors of survivalBetter predictors of survival• Severe dysfunction in latest phasesSevere dysfunction in latest phases• Extremely poor prognosis.Extremely poor prognosis.

PathogenesisPathogenesis

• Complex interaction between:Complex interaction between:• portal hypertension portal hypertension • circulatory dysfunctioncirculatory dysfunction• endogenous vasoactive systemsendogenous vasoactive systems• renal dysfunctionrenal dysfunction

• Backward Theory of Ascites FormationBackward Theory of Ascites Formation• Overflow Theory of Ascites FormationOverflow Theory of Ascites Formation• The Peripheral Vasodilatation HypothesisThe Peripheral Vasodilatation Hypothesis• The Forward Theory of Ascites FormationThe Forward Theory of Ascites Formation

Peripheral Arterial Peripheral Arterial Vasodilatation HypothesisVasodilatation Hypothesis

W ater R e ten tionS od iu m R eten tion

R en a l V asocon s tric t ionIn c rease in A rte ria l P ressu re

S tim u la tion o f:R en in -A n g io ten s in S ys tem

S ym p ath e tic N ervou s S ys temA rg in in e V asop ress in

A rte ria l U n d erfillin g

A rte ria l V asod la tion

P orta l H yp erten s ion

Hepatorenal SyndromeHepatorenal Syndrome• Occurs in the final phase of the cirrhosis.Occurs in the final phase of the cirrhosis.• Defined as:Defined as:

• ‘‘The development of renal failure in patients The development of renal failure in patients with severe liver disease in the absence of any with severe liver disease in the absence of any

other identifiable cause of renal pathology’other identifiable cause of renal pathology’• Prevelance:Prevelance:

• 4% of patients admitted with decompensated 4% of patients admitted with decompensated cirrhosis.cirrhosis.

Differential Causes of Renal Differential Causes of Renal FailureFailure

• DiureticsDiuretics• Ongoing Bacterial InfectionOngoing Bacterial Infection

• Spontaneous Bacterial PeritonitisSpontaneous Bacterial Peritonitis

• Nephrotoxic medications:Nephrotoxic medications:• Aminoglycosides, NSAIDS, ACE inhibitors, Aminoglycosides, NSAIDS, ACE inhibitors,

platinum derivatives platinum derivatives

• Circulatory compromiseCirculatory compromise• Variceal haemorrhageVariceal haemorrhage

• Rapidly progressing glomerulonephritisRapidly progressing glomerulonephritis

Diagnostic CriteriaDiagnostic Criteria• Chronic/acute liver disease with adv hepatic failure and Chronic/acute liver disease with adv hepatic failure and

portal hypertensionportal hypertension• Creatinine Creatinine 1.5 mg/dL 1.5 mg/dL • oror• 24hr Creatinine Clearance < 40 mL/min24hr Creatinine Clearance < 40 mL/min• No alternative renal pathologyNo alternative renal pathology• No improvement after diuretic withdrawal and expansion of No improvement after diuretic withdrawal and expansion of

plasma volume with 1.5 L of isotonic salineplasma volume with 1.5 L of isotonic saline• Proteinuria < 500mg/d and no ultrasonographic evidence of Proteinuria < 500mg/d and no ultrasonographic evidence of

obstructive uropathy or parencymal renal disease.obstructive uropathy or parencymal renal disease.• Urine Vol < 500 ml/dayUrine Vol < 500 ml/day• Urine NaUrine Na+ + < 10mEq/L< 10mEq/L• Urine osmolality greater than plasma osmolalityUrine osmolality greater than plasma osmolality

Evolution of Renal Evolution of Renal DysfunctionDysfunction

• Impaired renal sodium metabolism in Impaired renal sodium metabolism in compensated cirrhosiscompensated cirrhosis

• Sodium retention without activation of Sodium retention without activation of the RAAS or sympathetic NSthe RAAS or sympathetic NS

• Stimulation of the endogenous Stimulation of the endogenous vasoconstrictor systems with preserved vasoconstrictor systems with preserved renal perfusion and GFRrenal perfusion and GFR

• Development of Type-2 HRSDevelopment of Type-2 HRS• Development of Type-1 HRSDevelopment of Type-1 HRS

Treatment and ManagementTreatment and Management

• Bed Rest and Low Sodium DietBed Rest and Low Sodium Diet• Paracentesis and Fluid ManagementParacentesis and Fluid Management• Pharmacological TreatmentPharmacological Treatment

• Terlipressin Terlipressin - Vasopressin Analogue - Vasopressin Analogue • ParvolexParvolex - N-Acetylcysteine - N-Acetylcysteine• PentoxyphillinPentoxyphillin - Peripheral Vasodilator - Peripheral Vasodilator• Ursodeoxycholic acid - Treat 1Ursodeoxycholic acid - Treat 1o o biliary cirrhosisbiliary cirrhosis• Sando - K Sando - K - Treat potassium depletion - Treat potassium depletion• Multi-vitaminsMulti-vitamins

ProgressProgressDate Na+ K+ Urea Creatinine Bilirubin ALT 23/ 10 134 2.9 12.9 225 386 55 20/ 10 134 2.7 14.5 247 440 57 15/ 10 131 3.9 15.6 314 500 66 11/ 10 124 3.1 15.8 350 533 88 07/ 10 126 3.8 15.2 369 576 92

•Improvement in liver functionImprovement in liver function

•Improvement in renal functionImprovement in renal function

•Although on going electrolyte Although on going electrolyte disturbancedisturbance

•No unwanted effects observedNo unwanted effects observed

Creatinine ClearanceCreatinine Clearance

050

100150200250300350400450

1 2 3 4 5 6 7 8 9 11 13 14 15 16 17 18

Day Since Admission

Cre

atin

ine

(um

ol/l

)

Further ManagementFurther Management

• The only effective and permanent The only effective and permanent treatment for HRS is orthotopic liver treatment for HRS is orthotopic liver transplantationtransplantation

• Prognosis:Prognosis:• One year survival rate: 71%One year survival rate: 71%• Five year survival rate: 60%Five year survival rate: 60%