Hepatic failure and hepatorenal syndrome are characterized by liver dysfunction and associated kidney impairment. Portal hypertension and toxins that normally metabolized by the liver can accumulate in the brain, causing encephalopathy. Hepatorenal syndrome is classified as type 1 with rapid renal decline or type 2 with slower progression. It involves circulatory changes and activation of vasoactive systems. Treatment focuses on correcting precipitating factors, volume expansion, medications to constrict renal vasculature, and liver transplantation which is the definitive treatment. Dialysis may be used as a bridge to transplantation.

1. HEPATIC FAILURE &
HEPATORENAL SYNDROME

2. DEFINITION
• Portal-systemic encephalopathy is a complex organic brain syndrome
characterized by disturbances in consciousness, fluctuating neurologic signs,
asterixis or “flapping tremor” and distinctive electroencephalographic
changes.
• Acute and self-limiting or Chronic and progressive.

3. ETIOLOGY & PRECIPITATING FACTOR

4. • Chronic Parenchymal Disease
1. Chronic Hepatitis.
2. Cirrhosis
# Fulminant Hepatic Failure
1. Acute Viral Hepatitis
2. Drugs & Sedatives( Antipsychotics & Alchohol Intoxication)
3. Toxins e.g Wilson’s Disease

5. • Surgical Portal Systemic Anastomosis(Portocaval Shunt) TIPPSS
• Excessive Nitrogen Load –Excess protein consumption
Gastrointestinal Bleeding renal Failute Constipation.
• Electrolyte or Metabolic Distrubance Hyokalemia Hyponatremia
Alkalosis Dehydration Excess Vomiting
• Infection Pnumonia UTI SBP

6. PATHOGENESIS
• Shunting of Portal Blood Directly to Systemic Circulation Bypassing
liver.
• Severe Hepatocellular Damage & Dysfunction .
In both circumstances  Toxic Substance absorbed from intestine not
metabolized by liver Toxins accumulate in the brain.

7. Toxic Substances
• Ammonia
• Methionine
• Mercaptans
• Short Chain Fatty Acids
• GABA
• Octapamine
• False Neurotransmitter Substance

8. Ammonia Theory
• Ammonia -produced by the catabolism of amino acids involving 2 reactions:transamination
(catalysed by aminotransferases) oxidative deamination (catalyysed by L-amino acid oxidase).
• Normally, ammonia is detoxified in the liver by conversion to urea by the Krebs-Henseleit cycle.
Ammonia is also consumed in the conversion of glutamate to glutamine, a reaction that depends
upon the activity of glutamine synthetase.
• Two factors contributing to the hyperammonemia seen in cirrhosis.
1. decreased mass of functioning hepatocytes fewer opportunities for ammonia to be detoxified
by the above processes.
2. portosystemic shunting may divert ammonia-containing blood away from the liver to the systemic
circulation.
*Ammonia crosses the blood–brain barrier absorbed and metabolised by the astrocytes (cells in
the brain that constitutes 30% of the cerebral cortex).
*Astrocytes use ammonia when synthesising glutamine from glutamate.
*Increased levels of glutamine increase in osmotic pressure in astrocytesswelling of astrocytes.

9. Clinical Features
• Disturbance in Conciousness.
• Disturbacne in Sleep Pattern.
• Hypersomina is the Earliest Feature.
• Change in Personality
• Childish Behaviour.
• Irritabiltiy
• Aggressive
• Defecation & Urination at inappropriate
places.
• Fetor Hepaticus

10. Fetor Hepaticus
• Sour Musty Odour in the breath due to volatile substances normally
formed in the stool by bacteria.
• These mercaptanes if not removed by the liver are excreted through
the lungs and appear in the breadth.
• Fetor Hepaticus does not correlated with the degree or duration of
encephalopathy.

11. Clincial Features
• Fluctuating Neurological Signs
1. Slurred Speech
2. Hypertonia
3. Flapping Tremors
4. Exaggrated Tendon Reflexes
5. Bilateral Extensor Planter reflexes.

12. Diagnosis
• Usually one of exclusion.
1. Evidence of Advanced Hepatocellular Disease extensive
portosystemic collateral shunts or both.
2. Characteristic Clinical Features.
Forgetfullness & ConfusionStuporDeep Coma.
1. Fluctuating Neurological Signs.
2. Characteristic EEG Changes.

13. Investigation
• Diagnosis is usually clinically
1. No Liver Function abnormality.
2. Elevation of Blood Ammonia Level.
3. Hypokalemia.
4. EEG
5. CSF or CT SCAN
6. Visual Evoked Potential Abnormality in initial Stages.
7. Routine Investigation

14. Treatment
• Hospitalisation
• ABC Maintain
• Remove the cause and precipitating Factor.
• IV Fluid dextrose Saline and Injection thiamine.
• Maintainence of Fluid & Electrolytes & Calories.
• Ryle’s Tube Feeding and Urinary Catheterization.
• Diet Restriction of Protein diet & High Glucose Diet.
• Inj Vitamin K

15. • Avoid Constipation.
• Antibiotics(Neomycin, Ampicillin, Metronidazole, Rifaxamin)
• Liver Transplantation

16. Lactulose
• Non absorbable diasaccharide.
• Osmotic Laxative Effect.
• It Reduces ph of the colonic content and thereby prevents absorption
of NH3.

17. LOLA
• L-Orinithine-L-Aspartateis used to increase the generation of urea
through the urea cycle, a metabolic pathway that removes ammonia
by turning it into the neutral substance urea.
• It may be combined with lactulose and or rifaximin if these alone are
ineffective at controlling symptoms.

18. Complications
• Brain Herniation.
• Brain Edema
• Increased Risk of Cvs Collapse, Renal Failure, Respiratory Failure,
Sepsis.
• Permenanat Nervous system damage.
• Progressive Irreversible Coma
• Side effects of Medications.

19. HEPATORENAL SYNDROME
• It is syndrome that occurs in a patient with cirrhosis portal
hypertension and advanced liver failure characterized by imapaired
renal function with marked abnormalities in the arterial circulation
and activity of endogenous vasoactive system.
• Functional disorder.
• Kidneys are histologically normal.

20. IAC(International Ascites Club Criteria)
• Chronic or Acute Liver disease with advanced hepatic failure and portal
hypertension.
• Low GFR or Serum Creatinine >1.5 Mg/dl.
• Absence of shock, ongoing bacterial infections, and current or recent Rx
with nephrotoxic drugs.
• Absence of GI fluid losses.
• Absence of renal fluid losses in response to diuretic therapy.
• No sustained improvement in renal function after diuretic withdrawal and
expansion of plasma volume with 1.5 liters of isotonic saline.
• Proteinuria <500mg/day, and no USG e/o obstructive uropathy or
parenchymal renal disease.

21. • Minor Criteria
1. Urine volume <500ml/day.
2. Urine sodium <10mmol/L.
3. Urine osmolality > Plasma osmolality.
4. Serum Na <130mmol/L.
5. Urine RBC <50/hpf.

22. Types of Hepato Renal Syndrome
• Type I
Rapidly progressive reduction of renal function as defined by doubling
of the initial S.cr to a level >2.5 mg/dL in < 2 wk.
Clinical Pattern Acute Renal Failure.
• Type 2
Moderate renal failure (S.cr ranging from 1.5 to 2.5 mg/dL) with a
steady or slowly progressive course.
Clinical Pattern Refractory Ascites

23. Definition of
TYPE 1 & 2
HRS

24. Pathophysiology

25. Pathogenesis

26. MOSF

27. Prevention
• SBP: IV albumin administration.
• Severe acute alcoholic hepatitis: Oral pentoxyphylline.
• Low protein ascites: Norfloxacin as 1o SBP prophylaxis.
• Large volume paracentesis: IV albumin to prevent paracentesis
induced circulatory dysfunction (PICD).

28. Management
• Liver transplantation is the only definitive treatment option.
• Renal failure at time of transplant has poorer outcomes.
• Bridge to Liver Transplantation needed.

29. Initial Management
• Admission to monitored care setting with Vitals Monitoring.
• Central line placement for CVP helpful, not mandatory
• Routine blood and urine investigations
• Abdominal USG
• Diagnostic paracentesis
• Discontinue diuretics
• Plasma expansion with albuminEvaluation for Orthoptic liver
transplantation

30. Pharmacologic
Therapy

31. TIPSS
• Few studies available (case series).
• Decreases portal pressure and
consequently reduces renal
sympathetic activity.
• Improvement in renal function
and survival noted compared to
no treatment (but may take
several weeks).
• Careful patient selection needed
to optimize safety and efficacy.

32. Renal Replacement Therapy
• To be used in patients with an urgent indication of HD and for
patients with no response to vasoconstrictor therapy.

33. Artificial Hepatic Support
• Detoxification treatment ~ form of artificial extracorporeal liver
support.
• Considered to be a bridge to liver transplantation
• Liver dialysis devices
1. Molecular Adsorbents Recirculation System (MARS)
2. Single Pass Albumin Dialysis (SPAD).
3. Prometheus system.

34. Liver Transplantation
• Treats the causative organ dysfunction.
• 1 yr survival rate: not on HD – 78.8% , on HD – 73.7%.
• Decrease survival with s.cr at similar MELD scores .
• Similar 2 yr and 5 yr survival among non HRS and HRS LT.
• Beneficial outcomes with renal protective immunosuppression.

35. Liver Kidney Transplantation
• Usual norms::
Preoperative HRS/ ATN usually don’t need KTP .
Many times 1o renal disease can be managed medically.
FACTORS CONTRIBUTING RENAL FAILURE::
Improved medical management leading to better survival.
Long waiting time for transplant.
Post-LT calcineurin inhibitors.
Patients of HRS who required prolonged HD (> 4 - 8 wks) may require
KLT and better outcomes have been reported.

36. Summary Of
HRS
Management