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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Hepatic encephalopathy Hepatic encephalopathy Presentation Transcript

  • Hepatic Encephalopathy Dr Bikash Ranjan Praharaj Post Graduate, Dept of Pediatrics MKCG Medical College, Berhampur
  • • Definition • Etiology & classification • Pathogenesis • Precipitating factors • Clinical manifestation • Management • Outcome
  • 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
  • Characterized by  Disturbances in consciousness & behaviour  Personality changes  Fluctuating neurologic signs, asterixis or flapping tremor  Distinctive EEG changes
  • 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
  • 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
  • Pathogenesis Theories –Ammonia hypothesis – False neurotransmitters & AA imbalance – Increase permeability of BBB –GABA hypothesis – Others
  • The Urea Cycle Aspartate Transaminase(AST) Alanine Transaminase (ALT)
  • 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
  • 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
  • Which ultimately l/t Increase FNTs Decrease normal neurotransmitters Increase inhibitory neurotransmitters
  • False Neurotransmitter Hypothesis  AAA are precursors to neurotransmitters and elevated levels result in shunting to secondary pathways
  • 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
  • GABA hypothesis • Major inhibitory neurotransmitter. • Evidence: increased GABAergic tone & Flumazenil improves clinical outcome • Cause - Decrease hepatic metabolism - Increase gut wall permeability
  • 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.
  • Other neurotoxins • Mercaptans: Inhibit Na+-K+ ATPase • Short & medium chain fatty acids: inhibit Na+-K+ ATPase & Urea synthase • Phenol: a neurotoxin
  • Precipitating factors
  • CLINICAL MANIFESTATIONS
  • • 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
  • In MHE : • children have normal abilities of memory, language, construction & pure motor skills. • have normal standard mental status testing & abnormal psychometric testing.
  • Mild to moderate HE: • Decreased short term memory or forgetfulness • Loss of concentration & irritability • Asterixis, hyperventilation & hypothermia • Relative bradycardia (if ass. with increase ICP)
  • Clinical grading • West Haven classification system • Prognostic significance • Better in grade I & worse in grade IV
  • 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.
  • 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
  • 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
  • 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
  • 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
  • Investigations
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Proposed Complex Feedback Mechanisms In Treatment Of HE
  • 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
  • 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
  • Actions Of Lactulose
  • Bowel sterilization • Neomycin : orally through NGT dose: 50- 100mg/kg • Ampicillin • Rifaximin • metronidazole
  • Other measures • NGT aspiration • High colonic wash • Zn • L-Ornithine-L-Aspartate : oral/iv • Sodium Benzoate: 5g PO BD • H.Pylori eradication
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • Thanks