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Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
Hepatic encephalopathy
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Hepatic encephalopathy

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hepatich encephalopathy in children & its management with referrence from standard text books

hepatich encephalopathy in children & its management with referrence from standard text books

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  • 1. Hepatic Encephalopathy Dr Bikash Ranjan Praharaj Post Graduate, Dept of Pediatrics MKCG Medical College, Berhampur
  • 2. • Definition • Etiology & classification • Pathogenesis • Precipitating factors • Clinical manifestation • Management • Outcome
  • 3. Definition Hepatic encephalopathy (HE) is a complex metabolic mental state disorder with a spectrum of potentially reversible neuropsychiatric abnormalities seen in patients with severe acute or chronic liver dysfunction after exclusion of other brain diseases
  • 4. Characterized by  Disturbances in consciousness & behaviour  Personality changes  Fluctuating neurologic signs, asterixis or flapping tremor  Distinctive EEG changes
  • 5. Epidemiology  Exact data regarding incidence and prevalence is lacking  60-70% of patients with liver cirrhosis, while clinically unremarkable have pathologic changes on EEG and psychometric tests.(MHE)  Prevalence of minimal HE is about 53% in patients with extra hepatic portal vein obstruction  Approximately 50% of patients with liver cirrhosis develop HE after surgical portosystemic bypass procedures
  • 6. Type Description Subcategory Subdivision A Encephalopathy associated with acute liver failure, typically associated with cerebral edema _____ ______ B Encephalopathy with Porto-systemic bypass and no intrinsic hepatocellular disease _____ ______ C Encephalopathy associated with cirrhosis or portal hypertension ⁄ Porto-systemic shunts Episodic Persistent Minimal •Percipated •Spontaneous •Recurrent •Mild •Severe •Treatment dependent Classification
  • 7. Pathogenesis Theories –Ammonia hypothesis – False neurotransmitters & AA imbalance – Increase permeability of BBB –GABA hypothesis – Others
  • 8. The Urea Cycle Aspartate Transaminase(AST) Alanine Transaminase (ALT)
  • 9. Neurotoxic Action of Ammonia • Readily crosses blood-brain barrier • Ammonia reacts with α-ketoglutatrate to produce glutamate and glutamine • Consumption of α-ketoglutatrate, NADH and ATP, inhibition of pyruvate decarboxylase decrease TCA cycle activity which is vital for brain metabolism • Increased glutamine formation depletes glutamate stores which are needed by neural tissue l/t Irrepairable cell damage and neural cell death ensue. • Directly depress the cerebral blood flow & glucose metabolism • Direct toxic effect on the neuronal membrane
  • 10. False neurotransmitters & Aminoacid imbalance • BCAA/AAA (N= 3-3.5, In hepatic coma=0.6- 1.2) • BCAA : hyperinsulinemia  increased uptake & utilization by muscle & adipocytes • AAA : - insulin/glucagon --> catabolism of liver proteins & muscle --> AAA - Decrease hepatic deamination - Decrease gluconeogenesis
  • 11. Which ultimately l/t Increase FNTs Decrease normal neurotransmitters Increase inhibitory neurotransmitters
  • 12. False Neurotransmitter Hypothesis  AAA are precursors to neurotransmitters and elevated levels result in shunting to secondary pathways
  • 13. Increase Permeability of Blood-Brain Barrier • Astrocyte (glial cell) volume is controlled by intracellular organic osmolyte which is glutamine • Increase glutamine levels in the brain result in increase volume of fluid within astrocytes resulting in cerebral edema (enlarged glial cells) • Neurological impairment “Alzheimer type II astrocytosis” – Pale, enlarged nuclei – characterisic of HE
  • 14. GABA hypothesis • Major inhibitory neurotransmitter. • Evidence: increased GABAergic tone & Flumazenil improves clinical outcome • Cause - Decrease hepatic metabolism - Increase gut wall permeability
  • 15. Some other theories • Dysregulation of serotonergic system (inversion of sleep rhythm) • Depletion of zinc & accumulation of Mn in globus pallidus. • Action of cytokines and bacterial LPS on astrocytes which are formed d/t inflmm. elsewhere in the body. • Neuronal NO synthase may increase c/t the altered cerebral perfusion.
  • 16. Other neurotoxins • Mercaptans: Inhibit Na+-K+ ATPase • Short & medium chain fatty acids: inhibit Na+-K+ ATPase & Urea synthase • Phenol: a neurotoxin
  • 17. Precipitating factors
  • 18. CLINICAL MANIFESTATIONS
  • 19. • Variable & fluctuating • Mild disturbance of consciousness & altered behavior to deep coma • Psychiatric changes of varying degrees • F/o liver cell failure like flapping tremor & fetor hepaticus
  • 20. In MHE : • children have normal abilities of memory, language, construction & pure motor skills. • have normal standard mental status testing & abnormal psychometric testing.
  • 21. Mild to moderate HE: • Decreased short term memory or forgetfulness • Loss of concentration & irritability • Asterixis, hyperventilation & hypothermia • Relative bradycardia (if ass. with increase ICP)
  • 22. Clinical grading • West Haven classification system • Prognostic significance • Better in grade I & worse in grade IV
  • 23. Minimal encephalopathy • Defined as encephalopathy that does not lead to clinically overt cognitive dysfunction but can be demonstrated with neuropsychological studies. • May account for 60% of patients with portosystemic shunts.
  • 24. Clinical Manifestations & Diagnosis :MHE • Clinically normal • No mental deficit • Normal verbal ability • Deficit in attention ,visual perception, memory function, and learning • Impaired daily activities / driving • Only sophisticated tests such as EEG,CFF,ICT,NCT,DST, RBANS & PSE Syndrome test. • Neuroimaging : SPECT ,MRI,MRS.DWI
  • 25. Manifestations & Diagnosis :MHE Number Connection Test (NCT) 1 2 4 3 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 25 22 23 24 Begin End Time to complete____________________ Draw a star SAMPLE HANDWRITING
  • 26. Diagnosis of HE • No single laboratory test is sufficient to establish the diagnosis – No Gold Standard • Dx is mainly clinical on basis of history, clinical exam (includ mental status) & raised blood ammonia level
  • 27. Diagnostic Criteria • Asterixis (“flapping tremor”) • Hx liver disease • Impaired performance on neuropsychological tests – Visual, sensory, brainstem auditory evoked potentials • Sleep disturbances • Fetor Hepaticus • EEG • PET scan – Changes of neurotransmission, astrocyte function • Elevated serum NH3 – Stored blood contains ~30ug/L ammonia – Elevated levels seen in 90% pts with HE – Not needed for diagnosis
  • 28. Investigations
  • 29. Confirmation of liver disease/portosystemic shunt 1. LFT: increase in the following - Sr bilirubin/AST/ALT/ALP/GGT - PT(INR) > 1.5 with encephalopathy or >2 without encephalopathy - Sr protein, A:G ratio 2. Sr ammonia level is increased in most cases 3. USG
  • 30. Detection of causative factors • Viral serologic markers: HBs Ag, HBe Ag, anti-HBc, HBV DNA increased in Hepatitis • TORCH screening • Autoimmune ab: ANA, ASMA, LKM1 • Sr Cu, ceruloplasmin, urinary Cu : wilson’s disease • Urine for metabolic disorders • Sweat chloride & cystic fibrosis mutation studies • Alfa 1 antitrypsin levels : Alfa 1 antitrypsin def • Alfa feto protein : tyrosinemia type 1 • Sr lactate & pyruvate : GSD & resp chain defects • Liver biopsy: cirrhosis
  • 31. R/o other diseases with similar presentation • CT Scan: to r/o cerebral hemorrhage • EEG: r/o seizure disorder • CSF study: meningitis or encephalitis • Blood tests: metabolic causes of encephalopathy including hypoglycemia & uremia • Serum urea, Cr & electrolytes: renal failure
  • 32. Detection of complications • ABG- hypoxia is common • CBC: to r/o infection • Hb,PCV,CPS • PT, aPTT • Pt count decreased in advanced cases & coagulopathy • Blood glucose: hypoglycemia • Sr ammonia • RFT
  • 33. Differential Diagnosis Metabolic encephalopathies - Diabetes (hypoglycemia, ketoacidosis) - Hypoxia - Carbon dioxide narcosis Toxic encephalopathies - Alcohol (acute alcohol intoxication, delirium tremens, Wernicke- Korsakoff syndrome) - Drugs Intracranial events - Intracerebral bleeding or infarction -Tumor - Infections (abscess, meningitis) - Encephalitis Psychiatric diseases
  • 34. Treatment of Hepatic Encephalopathy • Various measures in current treatment of HE – Strategies to lower ammonia production/absorption • Nutritional management – Protein restriction – BCAA supplementation • Medical management – Medications to counteract ammonia’s effect on brain cell function • Lactulose • Antibiotics – Devices to compensate for liver dysfunction – Liver transplantation
  • 35. Proposed Complex Feedback Mechanisms In Treatment Of HE
  • 36. Diet • Decreased protein intake with high carbohydrates • Calorie in the form of 10%D infusion • Protein restricted to 0.5-1 g/kg/day • Veg protein preferred as they are less amminogenic , contain less amount of methionine & AAA and more fibres • Dietary supplementation of BAA • 50% of non-protein calories should come from MCT
  • 37. Lactulose/lactitol • Non absorbable synthetic diasachharide • Degraded by colonic bacteria to form lactic acid & acetic acid • Fecal acidity increase l/t decrease absorption of NH3 • Favours growth of lactose fermenting bacteria & diminished growth of ammo producing bacteria like bacteroides • Detoxify short chain FAs produced in presence of blood & proteins Dose: 1-2 ml/kg per orally or as enema in higher doses N:B:- Alternatively, phosphate enema can be used
  • 38. Actions Of Lactulose
  • 39. Bowel sterilization • Neomycin : orally through NGT dose: 50- 100mg/kg • Ampicillin • Rifaximin • metronidazole
  • 40. Other measures • NGT aspiration • High colonic wash • Zn • L-Ornithine-L-Aspartate : oral/iv • Sodium Benzoate: 5g PO BD • H.Pylori eradication
  • 41. Supportive care • Fluid & electrolyte balance: - Should contain 1meq/kg/d of glucose - Met acidosis: NaHco3 - Hypokalemia: pot. Chloride • Early identification & T/t of GI bleeding, septicemia & hypoxia • Avoidance of ppt factors: drugs/paracentesis • Drugs: To improve sensorium e.g Flumazenil, l-dopa, bromocriptine
  • 42. T/t in Resistant cases • Plasmapheresis/hemodialysis • exchange transfusion • Surgical shunt occlusion • Temporary hepatic support: - ELAD (Extracorporeal Liver Assist Devices) - MARS (Molecular Adsorbent Recirculating System) • Liver transplantation
  • 43. T/t of complications 1. CNS complications: • Cerebral edema: - Elevation of bed by 30 “,mannitol, hyperventilation & fluid restriction - Hypothermia & phenobarbitone • Seizures: phenytoin & gabapentin • Cerebral hypoxia: O2, N-acetylcysteine 2. Hypotension: colloids/albumin infusion 3. Bleeding: Inj Vit-k/ FFP/ Inj Ranitidine
  • 44. 4. Respiratory failure: - In Stage III & IV - Endotracheal Intubation 5. Renal Failure: - Furosemide in a dose of 1-2 mg/kg in early stages if CVP > 8-10 cm of H2O - Hemodialysis in established cases - Urine output should be maintained - Dopamine: Improve renal perfusion 6. Ascites: 5% albumin, bile acid binders
  • 45. Monitoring Protocol Daily Once in 3 days Weekly •Blood glucose (2 hrly) •Sr electrolytes: Na, K, HCO3- •Hb, PCV, CPS -Renal function tests -PT -NEC -Sr amino acids -EEG
  • 46. Minimal HE 1.No established indication for treatment 2.Consider changes in daily activities (avoid driving) 3.In selected patients • Lactulose /lactitol • Dietary intervention vegetable based diet • Probiotics
  • 47. Prophylaxis Of New Episodes 1.Control of precipitating factors 2.Nutritional support 3.Adequate protein intake with dairy and vegetable based diets 4.Vitamins 5.Zinc supplementation 6.Lactulose /lactitol as needed 7. OLT evaluation
  • 48. Course And Prognosis •Develops rapidly few hours – 1-2 days •Mortality in grade IV is 80% •Death usually due to brain herniation / edema ICH •Type C develops slowly – undulating course / recurrence •Neuropsychiatric manifestations are reversible •Can lead to permanent damage with dementia, extra pyramidal signs, cerebellar degeneration,myelopathy with spastic paraplegia, peripheral polyneuropthy •Liver TX can reverse all changes
  • 49. Prognostic indicators FEATURES GOOD PROGNOSIS BAD PROGNOSIS AGE CHILDREN ADOLESCENTS ETIOLOGY PCM POISONING, HEP A HEP C DURATION OF ENCEPHALOPATHY < 7 DAYS > 7 DAYS COMA GRADE I & II III & IV LIVER SIZE ENLARGED SHRINKING/NON PALPABLE BLEEDING TENDENCY ABSENT PRESENT FLUID RETENTION ---- +++ SR ALBUMIN N PT N PROLONGED LIVER ENZYMES: AST/ALT N AFP ASS. COMPLICATIONS ABSENT PRESENT IMPROVEMENT OF RAPID SENSORIUM WITH T/t NO IMPROVEMENT AFTER 48 HRS OF T/t
  • 50. Take home points • Ammonia is the main culprit • Dx mainly by clinical exclusion • Bad prognostic indicators: - Liver span - Bilirubin level - Liver enzyme levels - Prothrombin time • T/t of precipitating causes & supportive care is the mainstay of t/t • Prognosis bad in type A & better in other types
  • 51. Thanks

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